#ScienceSaturday posts share relevant and exciting scientific news with the KAND community. This project is a collaboration between KIF1A.ORG’s Research Engagement Team Leader Alejandro Doval, President Kathryn Atchley, Science Communication Volunteer Aileen Lam and Chief Science Officer Dr. Dominique Lessard. Send news suggestions to our team at email@example.com.
Detection of Low-Level Parental Somatic Mosaicism for Clinically Relevant Snvs and Indels Identified in a Large Exome Sequencing Dataset
What does it mean if someone is considered to be “genetically mosaic” or have “mosaicism”? Mosaicism is a situation where a person has two (or more!) genetically different sets of cells in their bodies. In the context of KAND, someone who has KIF1A mosaicism will likely have cells that have a KIF1A mutation and cells that do not have a KIF1A mutation. Until recently, genetic mosiacism was thought to be quite rare. However, as technology advances, and identifying cases of mosaicism becomes easier, some researchers suggest that mosaicism may contribute up to 6.5% of an individual’s genetic variation!
The paper we are featuring today dives into this concept by analyzing tissue samples for low levels of mosaicism in the body from a patient cohort. What makes their type of analysis different? These researchers are combining computational (computer aided) and molecular approaches that increase sensitivity and make it easy to find individuals with low levels of mosaicism. This study reveals that over 25% of their patient cohort had low levels of genetic mosaicism detected. When investigating which genes may be responsible for these high number of patients with mosaicism, one of their top findings was the KIF1A gene! In a way, this confirms a fact we are already aware of at KIF1A.ORG. On an anecdotal level, we have a growing cohort of community members who have been diagnosed with KIF1A mosaicism. This study helps us confirm that mosaicism, which was once thought to be quite rare, may not be very rare in the KAND or even wider rare disease community after all! Want to learn more about mosaicism? Check out the video below.
Committing to Care, Access, Equity and Research: NORD Announces 31 Rare Disease Centers of Excellence
Last week the United States National Organization for Rare Disorders (NORD) announced 31 official NORD Rare Disease Centers of Excellence! As defined by NORD, these centers represent a “nationwide network of cutting-edge facilities, with the goal to provide standards of specialized care and disease management for people living with rare disease and their families.” By establishing these centers of excellence, NORD can more effectively bring together leaders in the rare disease space to improve clinical care guidelines, expedite the referral and diagnostic process, and innovate new treatments. One of the selected NORD centers of excellence is Columbia University where our long-standing KAND clinical champion Dr. Wendy Chung and her team reside. Want to learn more about Dr. Chung and the precision medicine being conducted at Columbia University for rare disease patients? Have a look at the video below!
“Our belief is that the Center of Excellence program is the next big stride forward for rare disease treatment and patients – to improve health equity and create critical new connections to resources and specialists across our nation.”Ed Neilan, Chief Scientific and Medical Officer of NORD
Let’s talk about… Variants of uncertain significance
Advances in genetic testing are playing a significant role in our ability to pursue precision medicine. In the KAND community alone, we now know of over 100 disease-causing variants in the KIF1A gene that can lead to KIF1A Associated Neurological Disorder. As discussed above, we’re also finding more cases of mosaicism, in which a parent has a percentage of cells affected by a KIF1A mutation, but they do not have symptoms. This is still an extremely rare situation. What is more common in our community is seeing people with variants of uncertain significance, or VUSs.
While some KIF1A variants are clearly pathogenic (they cause KAND), others are benign. Not all KIF1A variants lead to KAND. But genetic test results are not always “black and white.” The medical and scientific community may not have enough information about particular KIF1A variants to determine whether or not it is responsible for a patient’s symptoms. This uncertainty can be extremely frustrating for caregivers and patients who are searching for answers. In some cases, as we learn more about KIF1A, classifications of particular variants may change. What was deemed a KIF1A VUS three years ago, may be upgraded to a pathogenic mutation today. Learn more about VUSs in this video from the National Health Service of England.