SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome

Shaw, Natalie D; Brand, Harrison; Kupchinsky, Zachary A; Bengani, Hemant; Plummer, Lacey; Jones, Takako I; Erdin, Serkan; Williamson, Kathleen A; Rainger, Joe; Stortchevoi, Alexei; Samocha, Kaitlin; Currall, Benjamin B; Dunican, Donncha S; Collins, Ryan L; Willer, Jason R; Lek, Angela; Lek, Monkol; Nassan, Malik; Pereira, Shahrin; Kammin, Tammy

doi:10.5167/uzh-141837

Citations

Citation copied

Shaw, N. D., Brand, H., Kupchinsky, Z. A., Bengani, H., Plummer, L., Jones, T. I., Erdin, S., Williamson, K. A., Rainger, J., Stortchevoi, A., Samocha, K., Currall, B. B., Dunican, D. S., Collins, R. L., Willer, J. R., Lek, A., Lek, M., Nassan, M., Pereira, S., … et al. (2017). SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome. Nature Genetics, 49, 238–248. https://doi.org/10.1038/ng.3743

Abstract

Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distin