#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 impact@kif1a.org.
KIF1A-Related Research
Illustration of a rare case of hereditary spastic paraplegia type 30 associated with a missense variant in the non‑motor domain of KIF1A
Similar to an article we shared in last week’s Science Saturday, this Letter to the Editor style paper tells the story of a 40-year-old patient diagnosed with a rare case of hereditary spastic paraplegia type 30 thought to be caused by a mutation in the KIF1A gene. While not initially diagnosed with KAND, this patient presented with many KAND symptoms starting as early as age 10, including irregular gait patterns, cognitive impairment, cerebellar atrophy and neuropathy. When whole-exome sequencing was performed on this patient, the results revealed a heterozygous KIF1A R1296H mutation (meaning only one of two KIF1A copies in this patient’s body has this specific mutation).
One aspect of this story that it a bit unique is the location of this mutation within the KIF1A protein. The majority of known KAND causing KIF1A mutations are located inside of the KIF1A motor domain (shown in the video below). The motor domain is the region of the protein that is responsible for helping KIF1A use cellular energy sources to facilitate KIF1A movement, one of its most important qualities in our neurons. However, the mutation highlighted in today’s paper is located outside of the motor domain. While we have less of an understanding of how mutations outside of the motor domain impact KIF1A function, it is clear (in part due to papers like the one we are featuring today) that they can cause clinical manifestations. Furthermore, we are learning about more and more KIF1A mutations outside of the motor domain every day as individuals join our community. To learn more about this patient report, click on the button below.
Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia
Continuing our theme of KIF1A’s role in cases of heredity spastic paraplegia (HSP), this second paper we are featuring today investigated the genetic causes of 1550 patients who have been clinically diagnosed with HSP. But first, what is HSP? HSP is a broad group of inherited neurological disorders that share the common symptoms of muscle weakness and tightening in the legs that can impair walking abilities. HSP is commonly diagnosed through clinical level tests such as MRI scans of the brain and spine, cerebrospinal fluid, nerve conduction tests, and patient history. However, like many similar diseases, there has been a recent rise genetic level testing (i.e. figuring out if specific gene mutations are linked to clinical disease) due to increased accessibility and availability in this type of diagnostic test.
Like we commonly see when genetic screens are performed on large clinical cohorts with neurodevelopmental or neurodegenerative symptoms, the KIF1A gene was one of the genes identified in this cohort of 1550 HSP patients, albeit one of the rarest genes identified, representing about 1% of patients sampled. From this study we get further confirmation of the significant role that the KIF1A gene plays in a broad range of neurodegenerative and/or neurodevelopmental disorders. Want to learn more about genetic testing? Check out the video below!
Rare Roundup
Rare Disease Drug Developers Raised $22.9 billion in 2021, a 28 Percent Increase over Previous Year
We may be rare, but we’re continuing to see pharmaceutical and biotech companies invest in therapeutic development to address the significant unmet needs of rare disease patients. This 2021 recap prepared by Global Genes sets an optimistic tone as we start the new year.
“Rare disease therapeutic developers continue to have a strong allure to investors and as evidenced by the significant amounts of capital they were able to raise in 2021 to advance their pipelines. The sector should continue to be strengthened by emerging technologies and the growing ability of rare disease therapeutics developers to not only provide meaningful treatments for conditions with unmet needs, but address the underlying cause of genetic diseases and provide functional cures.”
Global Genes, published January 11, 2022
ONCE UPON A GENE – Episode 116 – A Dads Fight to Survive Cancer and the Heavy Burdens of Rare Disease with Luke Rosen
“We can’t die.”
Luke Rosen, KIF1A Dad & KIF1A.ORG Co-Founder
Rare disease parents are terrified of dying. What will happen to my child? Who will care for them? Who will fight to find them treatment? If you haven’t listened to this Once Upon a Gene podcast with KIF1A dad Luke Rosen and rare mom Effie Parks yet, we are sharing it in this week’s Science Saturday. Spoiler alert: Luke is currently cancer free!