Compound heterozygous TRPV4 mutations in two siblings with a complex phenotype including severe intellectual disability and neuropathy

TRPV4 encodes a polymodal calcium‐permeable plasma membrane channel. Dominant pathogenic mutations in TRPV4 lead to a wide spectrum of abnormal phenotypes. This is the first report of biallelic TRPV4 mutations and we describe two compound heterozygous siblings presenting with a complex phenotype including severe neuromuscular involvement. In light of previously well described dominant inheritance for TRPV4‐related neuromuscular disease, our study suggests a role for compound heterozygosity and loss‐of‐function as a potential novel disease mechanism for this group of disorders. Profound intellectual disability was also noted in both affected children, suggesting that TRPV4 may be necessary for normal brain development.

Source: American Journal of Medical Genetics Part A - September 12, 2017 Category: Genetics & Stem Cells Authors: My Linh Thibodeau, Colin H. Peters, Katelin N. Townsend, Yaoqing Shen, Glenda Hendson, Shelin Adam, Kathryn Selby, Patrick M. Macleod, Cynthia Gershome, Peter Ruben, Steven J. M. Jones, , Jan M. Friedman, William T. Gibson, Gabriella A. Horvath Tags: CLINICAL REPORT Source Type: research