Talking to kids about genetic differences- Three great books to share

Talking to kids about genetic differences- Three great books to share

It can be difficult to explain complicated genetic topics to children with chromosomal differences, or to discuss a child’s uniqueness with family members, siblings, or even to curious strangers. Finding the right words can be even harder if your child is newly diagnosed, or if very little is known about what to expect in the future.

 The books summarized below address uniqueness, inclusion, even genetic/chromosomal differences. These frank, but endearing stories can better arm parents and caregivers with the language to talk about their child’s differences.

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A Rare Genomics patient is diagnosed using Genomenon’s Mastermind Search Engine

A Rare Genomics patient is diagnosed using Genomenon’s Mastermind Search Engine

Los Angeles, CA; February 27, 2019: Getting a diagnosis for a rare disease is a long and often painful journey that can take an average of five years and hundreds of doctor visits. Sometimes, the answer never comes; conventional diagnostics does not always provide a diagnosis for diseases that are only found in one in a million or one in 10 million people. Because most rare diseases are genetic in nature, genomic DNA sequencing can be used to provide answers that conventional approaches cannot.

Most families affected with rare diseases are under financial strain, making access to genetic sequencing technologies difficult. Rare Genomics Institute, a non-profit patient advocacy group, meets these patients at the end of their diagnostic odyssey – when all other means of diagnosis have failed and when financial resources are no longer available to continue the diagnostic process. Rare Genomics has created an ecosystem of leading technology partners and genetic experts from top research institutions around the world to give patients access to world-class genomic sequencing, data analysis and interpretation services. Often, Rare Genomics works with their partners and volunteer experts to re-analyze cases that have hit a dead end. 

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Bridging Health and Social Care for Rare Disease Day 2019

Bridging Health and Social Care for Rare Disease Day 2019

Rare Disease Day is held annually on the last day of February to raise awareness about rare diseases. This effort is targeted at the general public as well as those who influence legislation, research, and healthcare decisions that affect rare disease patients. The first Rare Disease Day took place on February 29, 2008. Since this day only occurs every four years on a leap year, it signifies the rarity of rare disease.

The theme of this year’s Rare Disease Day is “bridging health and social care”. This addresses the need for better coordination of all aspects of rare disease care including medical, social, and support services. The theme sheds light on how performing daily tasks can be difficult for rare disease patients and their caretakers. Activities such as cooking a meal, shopping, and cleaning the house can be difficult or impossible for someone with a disability.

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How The Orphan Drug Act Opened the Door for Rare Disease Research

How The Orphan Drug Act Opened the Door for Rare Disease Research

Drug research and development is a complicated process that the average person has little influence over and rarely thinks about. This is not the case for rare disease patients. Thoughts about how drugs are developed and why this process is so expensive are sure to come up more often for those affected by a rare disease. It can be a source of frustration since many pharmaceutical companies are reluctant to develop treatments for a rare disease.

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Giving Tuesday 2018 is Just Around the Corner

This Giving Tuesday, we hope you will consider making a donation to the Rare Genomics Institute (RG).

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We were able to complete 62 projects which includes whole genome sequencing for over 180 individuals. Our latest Patient team called the Rare Genomics Task Force (RGTF), a consultation platform that allows patients to have their questions answered by experts for free, provided consultations for over 200 patients.

Here at RG, we’ve had a busy year! Our volunteers donated over 18,000 hours of their time to help rare disease patients. We want to keep our momentum rolling this year and in years to come. Since RG is completely volunteer-run, the only way we can do this is with a donation from you.

A donation to RG will help a rare disease patient in need. Our patients often have no other options for access to genetic sequencing which can reveal the cause of their disease as well as potential research avenues or treatments.

Thank you for your generous support,

Jimmy Lin, M.D., PhD, MHD

President/CEO, Rare Genomics Institute

P.S. If you are buying holiday gifts on Amazon this year, please consider using our AmazonSmile link. At absolutely no additional cost to you, 0.5% of your purchase amount will be donated to RG. As a non-profit, volunteer-run organization, every cent really does help rare disease patients. Just click on the following link and then continue shopping as usual:

Rare Genomics is featured in the German Documentary, Medical Research on the Move

Last month the Nonfiction Society featured Rare Genomics Institute (RG) in a science documentary, which aired in German public television on September 13th, 2018. The documentary highlights “Medical research on the move, where organizations take initiative instead of blaming failing healthcare gaps or the pharmaceutical industry.” It is completely in German, but below is a synopsis of what RG contributed.

The documentary began by talking about the success of the Ice Bucket Challenge for ALS. It garnered over $100 million dollars of donations within a month of their campaign. During that time frame, over 28 million people joined the challenge by posting, commenting or liking a challenge post, Facebook said. Famed leaders and celebrities including Bill Gates, Charlie Sheen and Cristiano Ronaldo produced videos with about 16 million in views on YouTube at the time.

Through interviews with scientific experts worldwide, the documentary aimed to show the novel ways of funding medical research. They highlighted RG’s efforts for patients with rare diseases and interviewed Romina Ortiz, COO and VP of Patient Advocacy, to learn more about the Amplify Hope Study and current efforts by RG.

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Disorder: The Rare Disease Film Festival Returns to Boston

This September, The Rare Disease Film Festival returned to Boston for its second year. The event featured twelve films and trailers for future projects. Film topics were remarkably diverse, ranging from the charismatic account of an Epidermolysis Bullosa patient (This is Michelle) to a Hollywood production written by a young girl with mitochondrial disease (The Magic Bracelet).

A major theme of the event was how storytelling can give those struggling with a rare disease a powerful voice. Nicole Boice, founder of Global Genes, said that “storytelling can influence, impact, and inspire people to take action”.

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Pathway To Solving A Mystery

I have been a Genetics Analyst with the Rare Genomics Institute for over a year. The work that analysts like myself do is challenging, but we are aware of the impact and significance of our findings to the affected families. One of the services ( that we provide is to help identify mutated genes that are causing the patient’s symptoms, and if possible give a name to the disease. Our cases are typically undiagnosed where sequencing data is available.

Genome sequencing of the patient, siblings, and parents is carried out externally by one of our several partners, or the patient brings the sequence from previous analysis so we can re-interpret it. Whole Exome Sequence (WES) refers to sequencing only the DNA that encodes proteins, as opposed to whole genome sequencing (WGS), which includes non-protein encoding sequencing.  WGS and WES are preferred technologies over the more standard microarrays for diagnostic purposes. We currently do our analysis with WES exclusively and are planning to incorporate WGS in the near future.1

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Superstar Sunday: The Story of Mae

Mae is a beautiful, caring and creative 8 year old girl who loves dancing, swimming, baking and all things scientific. She has a sister nearly two years older than her.

We first noticed something wasn't quite right with Mae at around 2 years old when she was unable to jump or climb stairs easily as a toddler. Initially we just thought she had muscle weakness and weren't concerned at all. After doing the routine checks with the GP we ended up being referred to a physiotherapist to help develop 'strength' when she was 4 years old. After only 6 weeks the physio rang me to say that she thought I needed to take Mae to a pediatrician to have her assessed; I still, had no idea that anything could be 'wrong' with her. However, after one hour with the doctor, she told me that Mae had a muscle myopia and that she needed to be under the care of a neurologist and a number of other specialist.

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Living with Issacs’ Syndrome, a Rocky Story

A walk in the evening had left senior investment banking executive Tim Johnson in immense discomfort.

The 38-year-old based in Mumbai described a stabbing pain that had developed locally in the lumbar region and had extended to his right leg, which began cramping continuously. The next morning, the pain persisted and was accompanied with stiffness that made movements difficult. Johnson decided to consult an orthopedic specialist. It was February of 2016.

After being put on drugs with little to no improvement, Johnson consulted a gastroenterologist. He was then referred to a neurologist, and it was at this stage that Johnson received his first diagnosis of polymyositis, an inflammatory muscle disease.

Johnson’s month-long stay in the hospital involved running test after test to find a definitive diagnosis and careful deliberation of treatment. He was barely able to walk and dependent on painkillers taken three times a day. A month in the hospital left Johnson with no other choice but to resign from his investment banking work, which could not be left unattended to for so long.

By March 2016, Johnson’s team of medical experts had completed a thorough motor examination that had revealed average muscle status with wasting, stiffness in the upper limbs, excess weakness with spontaneous gross fasciculations in both arms and in some areas of the face. A nerve conduction study and EMG confirmed a final diagnosis—Isaacs’ Syndrome.

Also known as neuromyotonia, Isaacs’ Syndrome is a rare, muscle function disease currently affecting an estimated 100 to 200 people worldwide.

“It being a rare disease, the costs involved were very, very high,” said Johnson, who now works as a financial consultant. “In Indian Rupees, my bill was Rs 20 Lakhs [for hospitalization alone, about $31,000]. The rest of the costs, like travelling, were separate.”

Because the disease is so rare, Johnson has yet to meet anyone else with Isaacs’ Syndrome. But, he says he is part of a Facebook group for people suffering from it worldwide. Here, individuals can exchange ideas and share their stories.

“To be honest, I have been dealing with it alone,” said Johnson, who plans on posting in the Facebook group more often. “I am searching for a permanent solution and [trying] not to continue with symptomatic treatment only.”

Such symptoms that Johnson still deals with on a daily basis are commonly experienced among others with the disease and can occur when the peripheral nerves outside of the brain and spinal cord become easily excited, causing the muscle fibers they synapse with at the neuromuscular junction to continuously contract.1 This hyperexcitability leads to involuntary and constant muscle activity producing stiffness, cramping, and delayed relaxation, all of which can result in difficulty walking as well as fatigue.3

In a subset of cases, other symptoms may include excessive sweating, insomnia, seizures, constipation, and personality change, which may point to Morvan syndrome.3

The specific etiology of Johnson’s Issacs’ Syndrome remains unknown, but in many cases, it is either acquired or inherited genetically. In the case of acquired neuromyotonia, there is evidence suggesting the role of certain antibodies perturbing the normal functioning of voltage-gated potassium channels.2 These antibodies have been detected in 30-50% of patients.7 Neuromyotonia can also be triggered by an altered immune response to a neoplasm, or tumor, and is paraneoplastic in up to 25% of patients—often signaling potential thymus or lung cancer.7

While some cases of Isaacs’ Syndrome are acquired and may predate cancer, Isaacs’ Syndrome can be inherited as well. In 76% of patients with autosomal recessive axonal neuropathy with associated neuromyotonia (ARAN-NM), mutations in the histidine triad nucleotide-binding protein 1 (HINT1) gene on chromosome 5q31.1 were identified.4

“As far as I can recollect, there were no genetic tests performed,” Johnson wrote in an email. “PET scan was performed, and it showed no traces of cancer. [My] clinical manifestation of Isaacs’ Syndrome was typical.”

Today, Johnson is still managing his symptoms, which continue throughout the day and even during sleep. However, with a balance of medication, meditation, yoga, and walking, his symptoms have reduced in intensity. Aside from closely monitoring any changes due to medication or food, Johnson says he tries not to think about his disease too much.

Instead, he strives to keep a positive outlook on life by watching inspirational movies “again and again and again,” including the Rocky series.

“I have this quote: ‘Going in one more round when you don’t think you can – that’s what makes all the difference in your life’ by Rocky Balboa in my room,” Johnson said. “I see it first thing early morning and the day is history.”

Johnson says he views his disease both as an opportunity and responsibility to connect with more people and organizations, create awareness, and to learn more about himself.

“I wish and urge people to create the power of awareness and be a part of any social expedition to help others,” Johnson said. “Because of the position that I’ve been put in, I think it’s important to use my voice and people’s support to do as much as I can.”

The patient's name has been changed to maintain confidentiality


  1. UpToDate -Paraneoplastic syndromes affecting peripheral nerve and muscle, Josep Dalmau, MD, PhD and Myrna R Rosenfeld, MD, PhD
  2. Newsom-Davis J, Mills KR. Immunological associations of acquired neuromyotonia (Isaacs' syndrome). Report of five cases and literature review. Brain 1993; 116 ( Pt 2):453.
  3. (
  4. Ahmed A, Simmons Z. Isaacs syndrome: A review. Muscle Nerve 2015; 52:5.
  5. Tim’s pdf document
  7. Skeie, G. O., Apostolski, S., Evoli, A., Gilhus, N. E., Illa, I., Harms, L., Hilton-Jones, D., Melms, A., Verschuuren, J. and Horge, H. W. (2010), Guidelines for treatment of autoimmune neuromuscular transmission disorders. European Journal of Neurology, 17: 893–902. doi:10.1111/j.1468-1331.2010.03019.x

Rare Genomics earned the Platinum Seal of Transparency from GuideStar


Great news! Rare Genomics Institute just earned the Platinum Seal of Transparency from GuideStar, the world’s largest source of nonprofit information. By sharing these metrics, we’re helping the sector move beyond simplistic financial ratios to assess nonprofit progress. We’re proud to use GuideStar Platinum to share our full and complete story with the world. To reach the Platinum level, we added extensive information to our Nonprofit Profile: basic contact and organizational information; in-depth financial information; quantitative information about goals, strategies, and progress toward our mission. To learn more about GuideStar Platinum, go to

Personalized Medicine and Rare Disease

For those with a rare disease but without a diagnosis, almost all medicine is “precision medicine.” Whatever drugs or treatments they take are flexible if the patient or their doctors think that the symptoms could be treated with better drugs. In many cases genome sequencing allows for more specific and personalized treatments, and precision medicine has many applications.

In cancer treatment precision medicine means changing the drugs used in chemotherapy not only based on the type of cancer, but based on the mutations that make the cancer dangerous. In drug development, precision medicine means finding new drugs that act as “keys” to certain “locks” in the body. In someone with a rare disease, a diagnosis could lead to a life-changing treatment. But for many, science has not yet found a cure.

Without knowing the cause of the disease, it can be risky to decide which treatments to try on a patient. Sometimes, patients and doctors have no choice but to guess and check. Often patients and their doctors go through the complicated process of reverse engineering a treatment based on whether drugs provide relief or not. For example, if your muscles don’t function properly, there could be many things wrong at the cellular level. Drugs that target the nerve interacting with the muscle might not work, but drugs that target the muscle cells might. With this information, you know a little bit more about the disease, but it can months or years to settle on an optimal treatment with this method.

For some patient’s with rare diseases, genome sequencing opens the door for treating the exact cause disease, not just the symptoms. Continuing the example from above, something as complicated as your muscles could have dozens of reasons for not working properly. If a diagnosis pointed to a malfunctioning protein, treatment could be targeted around that protein. This approach of finding targetable defects has been used successfully in cancer patients.

Precision medicine is being increasingly utilized in cancer treatment. Doctors may request that genome of someone’s tumor be sequenced, to see if a silver-bullet medication is available. This would allow them to avoid using chemotherapy. Cancer is caused by genetic mutations, so sequencing can give doctors important information about how the cancer might develop and behave with certain treatments.

Research into cancer genomes is at the forefront of modern efforts to study and cure cancer. Once sequenced, the mutations in a patient’s cancer can be compared to those in a large database built by researchers. This could yield insight into treatment; some cancer drugs work better against specific mutations, and some treatments are ineffective for similar reasons. If applicable, the chemotherapy doses, timing, and even the drugs involved can be adjusted for the best results.

For some types of cancer, the risk of getting a tumor is hereditary. Genes that normally suppress tumor growth can be mutated, and passed on each generation. Genome sequencing can reveal inherited mutations such as these. Especially for those with a prominent family history of a certain cancer, sequencing can help a patient make informed decisions about their lifestyle. These patients will have informed discussions with their doctors about the prohibitive measures they should undertake, and what they would want in the event that they do get cancer. Often patients who know that they are at risk will have frequent screenings for tumors and stay away from habits like smoking, which can further increase their risk.

Another aspect of precision medicine is drug development. Developing new drugs is very difficult, expensive, and time consuming. Researchers might go through millions of compounds before finding a very specific “key” to a target enzyme’s “lock.” Even when this search is aided by computer modeling, which shows scientists the shape of the enzyme and possible drug compounds that could fit inside, finding even one possible drug is a daunting task.

Once a research team finds a few compounds that can block the targeted enzyme, they are tested for safety, and eventually are given to humans in a clinical trial. This development process takes a lot of time and resources as tests slowly scale up in size from a petri dish to a human being. After years of these tests the drug may go to clinical trial, where patients can sign up to participate in a study of the drug’s effectiveness. Years and many more tests after this the drug may get government approval and released to the general public. If the drug is safe, and works well, it may be approved for clinical use by the FDA.

Some of the bottlenecks for precision medicine include the cost, as well as privacy concerns. These designer drugs are usually only effective for a small cohort of patients, so to recover costs put into developing the drug, a pharmaceutical company may charge much higher prices than for other medicines. Also, like other health data, genetic information is private information, so security must be maintained for all patients.

While Rare Genomics mainly helps people get their exomes sequenced, they also seek to form communities of patients with rare diseases to share their experiences and scientific information. Along with other partners, RG makes information more accessible to patients with rare diseases and their families and seeks to support them post-diagnosis through programs like RareREACH and Rare Share.

Precision medicine was a science fiction goal of the future a short time ago. Today the practice helps countless patients receive higher quality care. With genome sequencing, precision medicine has expanded its reach and shown its potential, and with new technologies constantly in development, I wouldn’t be surprised if it could do even more.



Genomics and the Genetic Revolution

Rare diseases are difficult to diagnose. Years of tests, even targeted genetic tests, could give negative or inconclusive results. If something is wrong with your body then something might be wrong with the proteins that make it run. If something is wrong with your proteins then something is likely missing or added or replaced in your genes. But - how do you find out what that is?

One of the only ways to find a one in three billion “letter” difference in the books of your chromosomes is through genome sequencing. Relatively, genome sequencing hasn’t been around for very long.

DNA sequencing hasn’t been around for very long either.

In the 1970’s the first DNA sequencing tools were developed, and using a gel base, charge differences, and plenty of copied DNA strands, a computer could be used to calculate the sequence of nucleotides present on a short section of DNA.

This incredibly powerful tool allowed scientists to gather exact information about genes instead of just making very educated guesses. Still, improvements were needed. When DNA sequencing became available scientists predicted a world of personalized medicine and gene therapy, but up until 2003 even the most optimistic considered the predictions science fiction.

Public interest in genome sequencing picked up during the Human Genome Project in the 1990’s, a U.S. government initiative like the Apollo moon missions. The project sought to work with the best geneticists around the world so they could sequence the first full human genome.

The first genome fully sequenced was of a bacteriophage, an organism so small that it is just a pocket of protein with DNA inside. That genome was about 5,000 “letters” long, and sequencing was completed in 1977.

To put this in perspective, the calculations done to first land a man on the moon were done on slide rules, by hand. That restriction would make the human genome project nearly impossible.

Computing is the lifeblood of genome sequencing. The rise in efficiency of sequencing and reduction in cost is proportional to the rise in computing power. During the human genome project from 1990 - 2003, the internet took off, the .com boom took hold of the economy, all while amazon, eBay, and google were just startups working out the right formulas. In the midst of this rapid development computers were used to catalog and interpret the billions of nucleotides in the human genome.

The first cellular organism’s genome sequenced was the H. Influenza bacteria in 1995. The genome was one million base pairs long. In 1996, the first eukaryotic genome, a single celled organism with 12 million base pairs, was sequenced, and in 1998 the first animal genome, a nematode worm, was sequenced.

Nine years after scientists set out to sequence the entire human genome, the first human chromosome was sequenced.

By 2003 the Human Genome Project was completed. It had cost 2.7 billion dollars and took 13 years to sequence the full three billion base pairs. Still, the project was both under budget and ahead of schedule by two years. Today, 99% of a person’s genes can be fully sequenced for a price of $1,000, and can be completed in less than 24 hours.

Since the rapid growth in genome sequencing technology, the time needed to analyze the large amounts of data is now the barrier. For genetic diseases, especially rare ones, there is often only one “letter” difference between a healthy gene and a dysfunctional one. Imagine getting a textbook on everything you want to know, but it’s written in a foreign language. The massive amount of data provided by genome sequencing is a boon to science, but only when it can be interpreted.

Personalized medicine and diagnostics for genetic diseases were always a goal for genome sequencing. Before that could become a reality, the cost and time spent on sequencing had to come down. This was accomplished with the rise in computing and a more selective sequencing approach, looking at only the exome, which contains the protein coding sections of the genome. Sequencing finally made its way into the clinic in 2010, and the occasional sequencing of cancer genomes to allow for targeted treatments began even earlier.

While the cost of sequencing itself has gone down significantly, the price tag doesn’t include the many hours that are spent by specially trained geneticists to find a diagnosis. Human analysis, even aided by a computer, has always been a bottleneck of time and resources in genome sequencing.

The Rare Genomics Institute was founded in 2011. Rare Genomics connects families to research institutions and seeks to help families of rare disease patients crowdfund the resources needed for exome sequencing. By furthering the reach of genetic testing, RG helps to make genome sequencing more accessible to those in need. By expanding the reach of genetic testing, the boundaries of medicine are pushed along the lines of the “science fiction” goals set out before DNA sequencing was even available. I wouldn’t be surprised if those “science fiction” goals of genome sequencing were right around the corner.

Allyson "Ally" Lark - October Rare Bear

Ally Rare Bear.jpg

Allyson “Ally” Lark celebrated her 6th birthday at the end of August. Her family hails from Manitoba, Canada, approximately three-and-a-half hours away from Winnipeg by car. As in the photo with her Rare Bear, Ally is a happy kid. Her mother Madelaine “Leni” Lark describes Ally as an, “energetic, kind, spunky, beautiful, lovely little girl” whose likes include “horses, penguins, music, dancing, spending time with her big sister Bethany and the rest of her family.”

Ally has also been diagnosed with some physical conditions, which include Global Developmental Delay (GDD), Hypotonia and Soft Neurologic Signs (SNS). By utilizing genomic sequencing, it is the hope that Ally’s family can find more answers concerning the details of Ally’s conditions. Ally’s genetics and metabolism doctor (Dr. Patrick Frosk of the Children’s Hospital Research Institute of Manitoba), posits that Ally’s physical features are indicative of a metabolic disorder. Though genetic testing has not yet yielded a specific name for the disorder that Ally has, it is the hope of Ally’s family that as new developments and discoveries are made, Ally’s genetic information may be referenced and a more definite diagnosis may be reached soon.

A frustrating aspect of receiving the diagnoses that the Larks did when Ally was just two years old is the uncertainty of the developmental potential of their child. By contacting the Rare Genomics Institute and having sequencing performed, it is the hope that at least some of that uncertainty can be removed.

Ally's mother Leni described receiving Ally’s diagnosis, “we were very scared as her future at that point was unknown. We did not know what her developmental potential would be, and we did not know what to do, or where to start.”

Ally’s condition is a recognized disability in Canada. However, living nearly four hours from the nearest city has impacted the ability of the Larks to get the one-on-one care their daughter needs. Leni notes, “Resources (here) are so minimal for kids with disabilities. It is up to families and schools/daycares to provide therapies. This is frustrating because we are not able to access crucial resources for Ally as much as we would like, particularly speech therapy and PT…Despite all of this, Allyson has made tremendous gains!”

Like many of us, Ally does not enjoy going to the doctor. But on Boxing Day 2016, her mother contacted the Rare Genomics Institute in an attempt to get Ally the care she needed through the use of whole genomic sequencing. Ally did not qualify for sponsorship of this kind of genetic testing in her home province. However, the Rare Genomics Institute was happy to help the Lark family. Having been selected to receive Whole Exome Sequencing for their daughter, the Larks saved out-of-pocket costs that could have totaled more than $20,000.

The Lark’s experience with the Rare Genomics Institute has been a positive one. Though there is no answer at present as to why Ally has a developmental delay, her mother encourages all families in need of sequencing to reach out to Rare Genomics. Leni stated, “I would have regretted passing up this opportunity… (Rare Genomics is) great to work with! I was worried there would be a lot of red tape to go through as we are located in Canada and Rare Genomics is an American agency, but things went so smoothly.” The family’s plan now is to continue supporting their daughter any way they can. We at the Rare Genomics Institute are proud to have been a part of that support. If you or someone you know could benefit from whole genomic sequencing, please reach out to the Rare Genomics Institute via the links on this webpage.

Daryl Velez

The VanBrocklin’s are moving forward after Sequencing

As we pass the six-month mark as partners in the iHope program, it has already been so rewarding for us at Rare Genomics to see underserved families receive Whole Genome Sequencing in an effort to gain results and treatments for the conditions of their loved ones. We first shared the VanBrocklin story and video when they received their positive Whole Genome Sequencing results early this year.

I had the opportunity to interview the Van Brocklin family for the video at their home in Racine, Wisconsin, and came away very inspired. After visiting with Jami and Jonathan for just an afternoon, I was taken aback by all of the roadblocks that they have had to overcome in their search for answers for their children, Jasmine and Ronin. Now looking back months after receiving the sequencing results, we can see what a difference they have made.

The cost of copays, prescriptions and therapies for the VanBrocklin’s were well over $5,000 a year; in fact in 2016, they actually hit the threshold ceiling for medical tax deductions. With undiagnosed children, it was very difficult for the Van Brocklin’s to find any answers.  From a financial point of view, most insurance providers do not cover procedures like Whole Genome Sequencing, making it very difficult to acquire the comprehensive testing that is the key to unlocking these genetic secrets. From a parenting perspective, imagine having children with a disease that is unknown. It is impossible to start fighting a disease that you can’t even put a finger on.

Fortunately, both Van Brocklin children were able to take advantage of the iHope program and received results for their diseases. With Jasmine’s confirmed diagnosis for Ichthyosis Vulgaris, she has been referred by the Children’s Hospital of Wisconsin to their new pediatric genetic dermatologist.  This specialist possesses a much more thorough understanding of her condition. In Ronin’s case, with confirmed genetic testing findings of 16p11.2 microduplication he was able to obtain an official diagnosis of Autism. This diagnosis gives the Van Brocklin’s the option of specialized therapy, and also relieved concerns that his symptoms may have been due to a more significant health concern.

Our partners at Illumina, through the iHope program, have done a tremendous job working with us to provide underserved families with Whole Genome Sequencing testing and it has been a privilege of mine to be a small part of it.  If you are looking to be a part of the program, or if you have a family member that may qualify for the iHope program, please do not hesitate to join us in our search for answers.

Richard Bonds

Tenth Annual Rare Disease Day

The last day of February is a day to create awareness and let patients and affected with rare diseases be heard. This year, February 28th marks the tenth year of Rare Disease Day.

Rare Genomics (RG) participated last year, and we will again this year be a part of a day where rare diseases get the attention they deserve. This day patients worldwide stand together and make their voices heard, and RG wants to be a part of this.

What is Rare Disease Day?
Rare Disease Day seeks to raise awareness amongst both the general public and decision-makers about rare diseases and how living with these impacts patients’ lives.

Many different organizations participate in Rare Disease Day events. Rare Disease Day started in 2008 as a European phenomenon - but today it has expanded into be a worldwide phenomenon. Hundreds of patient organizations work to raise awareness for the rare disease community in their countries all year around, but on the last day of February they get extensive public and political attention.

The last day of February was chosen as Rare Disease Day since February 29th is the rarest day and only occurs every fourth year.

The official poster for Rare Disease Day 2017

Join us for Rare Disease Day
Rare Disease Day is an opportunity for RG to draw attention and awareness to rare diseases. The awareness is important in order to hopefully diagnose and cure many more patients with rare diseases in the future.

Please join us and participate in Rare Disease Day! Your donation to RG will help patients living with a rare disease. By donating to RG and being part of the tenth Rare Disease Day you contribute to a brighter future for the patients - a future without rare diseases.

Read more about Rare Disease Day and RG's participation here and donate by clicking the button below. Thank you!

Paper on Orphan Drug Development in China Published

Alice Cheng and Zhi Xie of the Rare Genomics Institute have published a open-access paper, "Challenges in orphan drug development and regulatory policy" in the Orphanet Journal of Rare Diseases.

Orphan drugs are pharmaceutical treatments developed to treat specific rare diseases. They aren't profitable for pharmaceutical companies to produce due to their extremely specific nature. Regulatory policies on orphan drug development are well-defined in the United States and European countries, but rare disease policies in China are still fluctuating. Pharmaceutical companies in China are de-incentivisted to pursue drug development for rare diseases due to a lack of clear definition and regulatory approval process. As a result, many rare disease patients in China pay out of pocket for international treatments.

Many grassroots movements have begun to support rare disease patients and facilitate research for the development of orphan drugs. The Chinese FDA has recently set new regulatory guidelines for drugs being developed in China, including an expedited review process for lifesaving treatments.

Cheng and Xie's paper compares orphan drug development and regulatory policy in China and the US. They find that due to political, economic, and cultural differences, China cannot simply base its policies on the American model. China's public healthcare system has the opportunity to take advantage of available data to create aggregated databases for diseases and genomic information, assisting epidemiology research.

The authors advocate for the five suggestions proposed by the National People's Congress and Chinese People's Political Consultative Conference of 2009:

  1. Establish a definition for rare diseases.
  2. Develop an orphan drug reimbursement system.
  3. Propose a clear and simple approval pathway for imported orphan drugs.
  4. Promte rare disease research through policy.
  5. Develop government-supported programs for rare disease patients.

Read the full paper from the Orphanet Journal of Rare Diseases.

Leading the Way: Marching Onward

At the Rare Genomics Institute, we understand that enacting change cannot happen unilaterally and that solving medical mysteries does not come without teamwork. We stand proudly at the forefront of the utilization of genomic sequencing for the purpose of identifying, treating and hopefully curing rare diseases. At the same time, we realize there are many other people outside of our organization who are just as fundamental to the fight against rare diseases as we are. The team at RG is inspired by those who dedicate their lives to helping others affected by rare disease. Here is one of their stories:

Research is the backbone of scientific discovery. Researchers do not often hone their craft in the spotlight: theirs is a task best suited at the lab bench, away from the public eye. It was, therefore, striking to come across a geneticist who works with the public on a daily basis as a pediatrician in my proverbial backyard at Columbia University. In December of 2016, I sat down with Dr. Wendy Chung to discuss her unique practice.

Dr. Chung holds both a PhD in genetics from Rockefeller University and an MD from Cornell University. The confluence of those pieces of education is not coincidental; “The year that I started my MD/PhD program was the year the Human Genome Project officially started. It became very clear to me that there was going to be a very unique opportunity in terms of being able to harness [that] power.”

Her interest in genetics in tow, Dr. Chung tailored her research and subsequent medical practice toward those who need genetic research most: children with rare diseases.

“A lot of individuals with rare disorders don't live to grow up,” Dr. Chung continued, “[However], it’s just been miraculous to me to be able to see how much things have evolved and changed in a very positive way: What I see now is that getting a diagnosis is much easier than it used to be. Now our energy needs to be focused on developing treatments. What drives me now is to figure out how we can get beyond the diagnosis and get to [those] treatments.”

Setting a Course:

The route that Dr. Chung’s lab takes toward diagnosis and treatment is somewhat irregular. Gene editing has been mentioned on the Rare Genomics Institute’s website before.

However, Dr. Chung edits the genes of model organisms (mostly mice) in order to test the reactions of those organisms to treatments before utilizing suggested treatments on humans. Dr. Chung’s practice is unique in that she and her team participate on both the research and practical implementation sides of the fence. She is actively both testing treatments and treating patients.

Dr. Chung stated, “We do everything we can in terms of clinical care and then we continue to march onward. If we don't find anything we can do clinically we cross over the fence into research mode and do everything we can on the research side. We can return information from the research study to [patients] and hopefully get them to a diagnosis faster and more effectively.”

Dr. Chung continued, “Because Columbia is a research institute, when we identify new conditions, we do our very best to help families connect to each other and to share information amongst clinicians. [We then] make that information freely available and accessible so that we can all learn together and try to understand mechanisms for why these conditions exist.” Dr. Chung detailed some of the limitations of more orthodox research methods, “If you're talking about cells in vitro, it’s a fine model for very basic molecules in terms of how they interact in a cell. But even if you make an organoid in terms of neurons in a dish, you can’t get that to function like a brain does. Maybe if you're lucky you'll get something that looks like a seizure from an electrical point of view, but often times you can’t get anything that approaches the right behavioral difference.”

Researchers at Columbia come to similar crossroads in Dr. Chung’s lab. “When it comes to mice or any other model organism,” stated Dr. Chung, “the mice may look basically fine, but the people, who have this same condition, they are clearly not fine.”

The two halves of Dr. Chung’s practice are united due to this complication. Though rodents inflicted with the same rare conditions as human patients may appear to function normally, Dr. Chung notes that mice do not read or write; they are not responsible for higher-order thinking challenges like those of a human. Therefore, sometimes, modeling is insufficient in both diagnosis and in research for treatment techniques for patients.

Next Steps:

The goal of Dr. Chung’s practice is, of course, not simply diagnosis but treatment. There are limitations to this goal, however. Research timelines often stymie a patient’s journey from diagnosis to treatment. Dr. Chung elaborates, “Treatment isn't something that comes a week after you get the diagnosis. It often takes several years to do that, but we're working with families to take that next step.”

Time is not the only limiting factor in the treatment of a patient living with a rare disease. Costs can be overwhelming for families. Accessibility is extremely important to the rare disease patient community and Dr. Chung’s team certainly recognizes the fact. Dr. Chung notes, “We take all types of insurance, whether it’s Medicaid or private insurance. We try to have enough capacity to try to deal with all of the different types of patients that would come in, whether they're kids or adults.”

“On the other hand,” Dr. Chung continued, “we also try to be realistic. If there are some individuals where, if we don’t think that there's a high enough probability that we're going to find something or help them even if we don't find an answer, we don't have them come halfway around the country.”

Working Together:

Dr. Chung’s patient population is wide-ranging in the geographic sense, and admission therein requires that only 3-5 patients are seen each week. Typical patients of the DISCOVER (Diagnosis Initiative: Seeking Care and Opportunities with Vision for Exploration and Research) Program “tend to be many of the same types of folks that you guys are working with at the Rare Genomics Institute” states Dr. Chung, “[these] kids may have neuro-developmental disorders or congenital anomalies or very rare or very early onset presentations of conditions that increase the probability that [their conditions may be] something hereditary.”

Many of Dr. Chung’s patients are designated “N-of-1” or the very first patients to experience certain conditions. Dr. Chung clarified, “Although it’s not always the case, it’s not unusual for us to be an N-of-1 situation for a while. [These situations] don’t stay N-of-1 for very long, but they often start out that way.”

The uniqueness of her patient’s conditions often leads to frustrations in treatment. Dr. Chung notes that in terms of ultra-rare diseases, the challenges of both time and money weigh heavily on the patient population, “ultra-rare diseases are individually so rare that it is hard to be able to get the resources and the talented scientists to be able to dedicate all their energies for conditions that affect one in two million people, for example.”

Emphatically reinforcing why her organization is important in the many fights against rare conditions, Dr. Chung stated, “Unless every rare disease is blessed with a family who has gazillions of dollars they don't know what to do with, you can get stuck.”

But Dr. Chung’s team needn’t help families get un-stuck alone, “This is very much a partnership. Families really have to take up the cause and push things forward, especially when it comes to the ultra-rare disorders. If they don't, it's not like a lot of people are going to run to their assistance.”

Moving forward from diagnosis is a communal effort: it is up to all of us. Whether you’ve been inspired by the work of artists or you know someone living with a rare disease yourself, the work of doctors and researchers to help patients living with rare conditions cannot be completed without your help. Please consider suppporting ongoing rare disease research efforts. Let's march onward together.

CRISPR and Gene Therapy: An Overview of the Breakthrough Gene-Editing Tool

CRISPR has been in the news lately—for good reason. At Sichuan University, the first human patient is being treated with immune cells edited via CRISPR.

CRISPR has made effective gene therapy a realistic possibility for the near future. But how?

The structure of Cas9, from the National Institutes of Health (NIH).

The structure of Cas9, from the National Institutes of Health (NIH).

Targeting DNA with CRISPR

CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats. The long name describes what it is: DNA segments from prokaryotes (single-cell organisms) with a series of short, repetitive base sequences punctuated by spacer DNA that originated from plasmids or phages (infectious agents). Palindromic repeats aren’t like palindromes in language; instead, they are a particular sequence of DNA that, when transcribed, can form a three-dimensional “hairpin” loop in RNA.

CRISPR DNA segments are part of a prokaryotic immune system, the CRISPR/Cas system. When plasmids and phages attack a prokaryote, inserting foreign DNA, this system resists. CRISPR associated proteins (Cas) use the foreign origins of CRISPR’s spacer DNA to identify the newly inserted sequences. Cas then copies these sequences and places them into an RNA molecule. Cas and this RNA molecule comb through the cell to find foreign DNA from plasmids or phages. When a match occurs, the portion of the RNA molecule copied from the spacer DNA locks on, allowing a Cas enzyme—Cas9, an endonuclease—to slice the foreign DNA. Now damaged from broken phosphodiester bonds, the plasmid’s or phage’s DNA can’t replicate within the cell.

The specific CRISPR/Cas system used in biotechnology is engineered from the CRISPR/Cas system in the bacteria that causes strep throat, Streptococcus pyogenes. When people talk about CRISPR, they’re referring to the whole CRISPR/Cas system, not just CRISPR as the DNA segments.

Using CRISPR to Cure

CRISPR can be used in gene therapy to treat diseases with a genetic component. Gene therapy uses genes themselves as a means to prevent or treat diseases. This can be done at a cellular level by inserting healthy genes, making a harmful gene inactive, or replacing a harmful gene with a healthy gene. Gene therapy uses a process called genome editing, which refers to any method that uses an endonuclease (molecular scissors) to cut DNA at a specific location in order to insert, remove, or replace a gene. Cas9’s ability to slice foreign DNA at targeted points makes CRISPR an effective tool for gene editing, and therefore, gene therapy.

When treating disease, scientists program CRISPR to detect a specific sequence that makes up a harmful gene. When that sequence is found, the DNA strand is unzipped and the harmful gene removed. In some cases, the DNA can repair itself. In others, scientists insert a healthy gene into the gap left by CRISPR. Gene therapy that occurs in somatic cells (body cells) facilitates treatment, as the gene’s intended function is restored.

Looking Forward

CRISPR isn’t foolproof, though; sometimes, Cas9 can cut DNA at the wrong place. However, CRISPR’s efficiency and overall accuracy allow it to overshadow earlier gene editing tools, like TALENs (transcription activator-like effector nucleases) and ZFN (zinc finger nuclease). Because of its programmable nature, it only takes a few days to engineer CRISPR to detect a specific sequence of DNA. With CRISPR, both copies of a gene—and both copies of multiple genes—can be edited at the same time.

Despite these qualities that make CRISPR the most efficient gene editing tool yet, both technical and ethical issues compound research. A significant technical hurdle is how CRISPR is delivered into individual cells. CRISPR must have direct access to a cell’s DNA to make repairs.

And even though CRISPR has already been used successfully in crops, mice, and mosquitoes, ethical questions arise when genetic engineering is applied to humans. This type of gene editing still poses risk: the crux of the decision to use gene therapy relies on weighing the risks of a genetic disease versus the risks of its potential cure. Even if ongoing research trials are successful, it will take years for CRISPR-enabled gene therapy to become a fixture of the clinician’s office.

Overall, CRISPR is an accurate and powerful tool revolutionizing how gene editing and gene therapy are approached. As more research is completed, the full potential of this method can be revealed.