• PMID: 20887963
• Gene Name: NR5A1
• Condition: Infertility
• Association: The data in this study increases the spectrum of phenotypes that are associated with mutations in NR5A1.
• Mutation: p.Gly123Ala (c.368G>C),p.Pro129Leu (c.386C>T), p.Gly146Ala, p.Asp238Asn (c.712G>A), p.Gly123Ala (c.368G>C), p.Pro131Leu (c.392C>T), p.Arg191Cys (c.571C>T), p.Gly212Ser (c.634G>A)
• Population size: 2433
• Population details: 2433 (315 unexplained infertility, 1064 DNA samples from 52 world wide populations, 140 French men, 89 men of West African origin, 96 men of North African origin, 370 fertile men, 331 European descent, 140 North African, 63 West African, 156 Indians, 30 E
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Azoospermia, Oligozoospermia, cryptozoospermia

Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1

Bashamboo A, Ferraz-de-Souza B, Lourenço D, Lin L, Sebire NJ, Montjean D, Bignon-Topalovic J, Mandelbaum J, Siffroi JP, Christin-Maitre S, Radhakrishna U, Rouba H, Ravel C, Seeler J, Achermann JC, McElreavey K.

One in seven couples worldwide are infertile, and male factor infertility accounts for approximately 30%-50% of these cases. Although many genes are known to be essential for gametogenesis, there are surprisingly few monogenic mutations that have been conclusively demonstrated to cause human spermatogenic failure. A nuclear receptor, NR5A1 (also called steroidogenic factor 1), is a key transcriptional regulator of genes involved in the hypothalamic-pituitary-steroidogenic axis, and it is expressed in the steroidogenic tissue of the developing and adult human gonad. Mutations of NR5A1 have been reported in 46,XY disorders of sex development and in 46,XX primary ovarian insufficiency. To test the hypothesis that mutations in NR5A1 cause male infertility, we sequenced NR5A1 in 315 men with idiopathic spermatogenic failure. We identified seven men with severe spermatogenic failure who carried missense mutations in NR5A1. Functional studies indicated that these mutations impaired NR5A1 transactivational activity. We did not observe these mutations in more than 4000 control alleles, including the entire coding sequence of 359 normospermic men and 370 fertile male controls. NR5A1 mutations are found in approximately 4% of men with otherwise unexplained severe spermatogenic failure. CI - Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. FAU - Bashamboo, Anu AU - Bashamboo A AD - Human Developmental Genetics, Institut Pasteur, 75724 Paris, France. anu.bashamboo@pasteur.fr FAU - Ferraz-de-Souza, Bruno AU - Ferraz-de-Souza B FAU - Lourenço, Diana AU - Lourenço D FAU - Lin, Lin AU - Lin L FAU - Sebire, Neil J AU - Sebire NJ FAU - Montjean, Debbie AU - Montjean D FAU - Bignon-Topalovic, Joelle AU - Bignon-Topalovic J FAU - Mandelbaum, Jacqueline AU - Mandelbaum J FAU - Siffroi, Jean-Pierre AU - Siffroi JP FAU - Christin-Maitre, Sophie AU - Christin-Maitre S FAU - Radhakrishna, Uppala AU - Radhakrishna U FAU - Rouba, Hassan AU - Rouba H FAU - Ravel, Celia AU - Ravel C FAU - Seeler, Jacob AU - Seeler J FAU - Achermann, John C AU - Achermann JC