title: Identification of NR5A1 Mutations and Possible Digenic Inheritance in 46,XY Gonadal Dysgenesis.
abstract: The phenotypic spectrum of patients carrying NR5A1 mutations ranges from 46,XY gonadal dysgenesis to male infertility. Phenotypic variability could be due to digenic or oligogenic inheritance of pathogenic variants in other testis-determining genes. Here, exome sequencing identified 2 pathogenic de novo NR5A1 mutations in 2 patients with 46,XY gonadal dysgenesis, p.Q206Tfs*20 and p.Arg313Cys. The latter patient also carried a missense mutation in MAP3K1. Our data extend the number of NR5A1 gene mutations associated with gonadal dysgenesis. The combination of an NR5A1 mutation with a MAP3K1 variant may explain the phenotypic variability associated with NR5A1 mutations.
authors.affiliation: Department of Clinical Genetics, National Research Center, Cairo, Egypt.
authors.forename: Inas
authors.initials: I
authors.lastname: Mazen
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Hamid
authors.forename: Mona
authors.initials: M
authors.lastname: Mekkawy
authors.forename: Joëlle
authors.initials: J
authors.lastname: Bignon-Topalovic
authors.forename: Radia
authors.initials: R
authors.lastname: Boudjenah
authors.forename: Mona
authors.initials: M
authors.lastname: El Gammal
authors.forename: Mona
authors.initials: M
authors.lastname: Essawi
authors.forename: Anu
authors.initials: A
authors.lastname: Bashamboo
authors.forename: Ken
authors.initials: K
authors.lastname: McElreavey
mesh_terms: D000328:Adult; D002675:Child, Preschool; D059472:Exome / Q000235:genetics; D005260:Female; D006059:Gonadal Dysgenesis / Q000235:genetics; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D054339:Steroidogenic Factor 1 / Q000235:genetics*
chemical_list: C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human