title: Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic failure in a Turkish family.
abstract: Infertility is a global healthcare problem, and despite long years of assisted reproductive activities, a significant number of cases remain idiopathic. Our currently restricted understanding of basic mechanisms driving human gametogenesis severely limits the improvement of clinical care for infertile patients. Using exome sequencing, we identified a nonsense mutation leading to a premature stop in the TEX15 locus (c.2130T>G, p.Y710*) in a consanguineous Turkish family comprising eight siblings in which three brothers were identified as infertile. TEX15 displays testis-specific expression, maps to chromosome 8, contains four exons and encodes a 2789-amino acid protein with uncertain function. The mutation, which should lead to early translational termination at the first exon of TEX15, co-segregated with the infertility phenotype, and our data strongly suggest that it is the cause of spermatogenic defects in the family. All three affected brothers presented a phenotype reminiscent of the one observed in KO mice. Indeed, previously reported results demonstrated that disruption of the orthologous gene in mice caused a drastic reduction in testis size and meiotic arrest in the first wave of spermatogenesis in males while female KO mice were fertile. The data from our study of one Turkish family suggested that the identified mutation correlates with a decrease in sperm count over time. A diagnostic test identifying the mutation in man could provide an indication of spermatogenic failure and prompt patients to undertake sperm cryopreservation at an early age.
authors.affiliation: Département Génomique fonctionnelle et cancer and Centre Hospitalier Universitaire, 67000 Strasbourg, France.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Okutman
authors.affiliation: Département Médecine translationelle et neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg, 67404 Illkirch, France, Laboratoire de diagnostic génétique, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Muller
authors.affiliation: Biology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Yoni
authors.initials: Y
authors.lastname: Baert
authors.affiliation: Bahceci Health Group, 34365 Sisli, Istanbul, Turkey.
authors.forename: Munevver
authors.initials: M
authors.lastname: Serdarogullari
authors.affiliation: Bahceci Health Group, 34365 Sisli, Istanbul, Turkey.
authors.forename: Meral
authors.initials: M
authors.lastname: Gultomruk
authors.affiliation: Département Médecine translationelle et neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg, 67404 Illkirch, France, Laboratoire de diagnostic génétique, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Piton
authors.affiliation: Biology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rombaut
authors.affiliation: Médecine de la Reproduction et Cytogénétique Médicale CHU et Faculté de Médecine, Université de Picardie Jules Verne, 80000 Amiens, France and.
authors.forename: Moncef
authors.initials: M
authors.lastname: Benkhalifa
authors.affiliation: Département Génomique fonctionnelle et cancer and Centre Hospitalier Universitaire, 67000 Strasbourg, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Teletin
authors.affiliation: Département Génomique fonctionnelle et cancer and.
authors.forename: Valerie
authors.initials: V
authors.lastname: Skory
authors.affiliation: Unimed Center, 34365 Sisli, Istanbul, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Bakircioglu
authors.affiliation: Biology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Goossens
authors.affiliation: Bahceci Health Group, 34365 Sisli, Istanbul, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Bahceci
authors.affiliation: Département Génomique fonctionnelle et cancer and Centre Hospitalier Universitaire, 67000 Strasbourg, France, viville@igbmc.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Viville
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D018389:Codon, Nonsense; D003241:Consanguinity; D059472:Exome; D020022:Genetic Predisposition to Disease; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology; D008297:Male; D008540:Meiosis; D009845:Oligospermia; D009929:Organ Size; D010375:Pedigree; D017422:Sequence Analysis, DNA / Q000379:methods*; D013091:Spermatogenesis; D013737:Testis / Q000033:anatomy & histology; D013997:Time Factors; D014421:Turkey; D044465:White People / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; C578814:TEX15 protein, human