Familial Hypocalciuric Hypercalcemia Type 1 and Autosomal-Dominant Hypocalcemia Type 1: Prevalence in a Large Healthcare Population

The calcium-sensing receptor (CaSR) regulates serum calcium concentrations. CASR loss- or gain-of-function mutations cause familial hypocalciuric hypercalcemia type 1 (FHH1) or autosomal-dominant hypocalcemia type 1 (ADH1), respectively, but the population prevalence of FHH1 or ADH1 is unknown. Rare CASR variants were identified in whole-exome sequences from 51,289 de-identified individuals in the DiscovEHR cohort derived from a single US healthcare system. We integrated bioinformatics pathogenicity triage, mean serum Ca concentrations, and mode of inheritance to identify potential FHH1 or ADH1 variants, and we used a Sequence Kernel Association Test (SKAT) to identify rare variant-associated diseases.

Source: The American Journal of Human Genetics - May 6, 2020 Category: Genetics & Stem Cells Authors: Ridge Dershem, Caroline M. Gorvin, Raghu P.R. Metpally, Sarathbabu Krishnamurthy, Diane T. Smelser, Fadil M. Hannan, David J. Carey, Rajesh V. Thakker, Gerda E. Breitwieser, Regeneron Genetics Center Tags: Article Source Type: research