Author Interviews, Genetic Research, Nature / 17.01.2017
Craniofacial Abnormalities and Rare Muscular Dystrophy Linked To Same Gene
MedicalResearch.com Interview with:
Natalie Shaw, MD, MMSc
National Institute of Environmental Health Sciences
Research Triangle Park, North Carolina and
Harrison Brand, PhD
Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research
Massachusetts General Hospital, Boston
Massachusetts, USA.
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Congenital arhinia, or absence of the nose and olfactory system, is an extremely rare malformation, often accompanied by defects in the eyes and reproductive system. Arhinia has been reported in only 80 patients in the past century and though a genetic cause had been suspected, no previous study had identified a plausible genetic candidate.
Through an international collaboration among clinicians and investigators spanning 10 different countries, we were able to assemble a cohort of 40 arhinia patients. Using whole-exome sequencing, we found that 84% of the patients had rare mutations in the same gene – SMCHD1. Further, modeling studies based on patient cells and SMCHD1 knockdown in zebrafish strongly support a role for the gene in arhinia.
We were surprised by this discovery because mutations that impair SMCHD1 function are known to interact with other regions of the genome to cause a type of muscular dystrophy (FSHD2) that does not affect the bones or cartilage of the face. Deep phenotyping of our cohort revealed that individuals with arhinia can in fact develop FSHD2, but it is still unclear why individuals with FSHD2 do not have arhinia.
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