title: Two Novel TEX15 Mutations in a Family with Nonobstructive Azoospermia.
abstract: OBJECTIVE
  Genetic investigations explain only a small percentage of cases of nonobstructive azoospermia (NOA), a condition that affects up to 2% of infertile couples. This study aimed to identify further genomic variants that are associated with primary spermatogenic failure within the testis.
  
  
  METHODS
  One family with 2 infertile siblings affected by NOA was genotyped by whole-exome sequencing. DNA variants were filtered based on quality score, allele frequency, and functional roles of genes in spermatogenesis.
  
  
  RESULTS
  Both NOA males were compound heterozygotes for a nonsense mutation and a single nucleotide deletion leading to premature stop codons in the TEX15 gene (c.2419A>T, p.Lys807*, and c.3040delT, p.Ser1014Leufs*5, respectively). The single mutations were identified only on one allele in 6 family members, including 3 fertile males who conceived naturally.
  
  
  CONCLUSIONS
  This is the second reported case of a TEX15 deleterious mutation cosegregating with NOA in a family in which the infertile phenotype is reminiscent of the one observed in the TEX15-knockout mouse, confirming that TEX15 plays a critical role in normal spermatogenesis and its defects may be responsible for a number of NOA cases.
authors.affiliation: Center for the Study of Rare Hereditary Diseases, Niguarda Ca' Granda Metropolitan Hospital, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Colombo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pontoglio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bini
mesh_terms: D000483:Alleles; D000818:Animals; D053713:Azoospermia / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D010641:Phenotype; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis
chemical_list: D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; C578814:TEX15 protein, human
keywords: Infertility; Loss of function; Molecular diagnosis; Mutation; Nonobstructive azoospermia; Pedigree; Reproductive medicine; Spermatogenic failure; TEX15 gene; Whole-exome sequencing