Homozygous Loss-of-function Mutations in SOHLH1 in Patients With Nonsyndromic Hypergonadotropic Hypogonadism

Context: Hypergonadotropic hypogonadismpresents in females with delayed or arrested puberty, primary or secondary amenorrheadue to gonadaldysfunction, and is further characterized by elevated gonadotropinsand low sex steroids. Chromosomal aberrations and various specific gene defects can lead to hypergonadotropic hypogonadism. Responsible genes include those with roles in gonadaldevelopment or maintenance, sex steroidsynthesis, or end-organ resistance to gonadotropins. Identification of novel causative genes in this disorder will contribute to our understanding of the regulation of human reproductive function. Objectives: The aim of this study was to identify and report the gene responsible for autosomal-recessive hypergonadotropic hypogonadismin two unrelated families. Design and Participants: Clinical evaluation and whole- exome sequencingwere performed in two pairs of sisters with nonsyndromic hypergonadotropic hypogonadismfrom two unrelated families. Results: Exome sequencinganalysis revealed...