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

作者：Thibodeau My Linh; Peters Colin H; Townsend Katelin N; Shen Yaoqing; Hendson Glenda; Adam Shelin; Selby Kathryn; Macleod Patrick M; Gershome Cynthia; Ruben Peter; Jones Steven J M; Friedman Jan M; Gibson William T; Horvath Gabriella A^*

来源：American Journal of Medical Genetics, Part A, 2017, 173(11): 3087-3092.

DOI：10.1002/ajmg.a.38400

• brachydactyly
• channelopathy
• hearing loss
• intellectual disability
• neuromuscular diseases
• peripheral neuropathy
• retinopathy
• scoliosis
• skeletal
• TRPV4

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.

• 出版日期2017-11