title: Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia.
abstract: BACKGROUND
  Azoospermia is the absence of a measurable level of spermatozoa in the semen. It affects approximately 1% of all men, and the genetic basis of the majority of idiopathic cases is unknown. We investigated two unrelated consanguineous families with idiopathic azoospermia. In family 1, there were three azoospermic brothers and one oligozoospermic brother; and in family 2, there were three azoospermic brothers. Testis biopsy in the brothers in family 2 had led to the diagnosis of maturation arrest in the spermatid stage.
  
  
  METHODS
  Candidate disease loci were found via linkage mapping using data from single nucleotide polymorphism genome scans. Exome sequencing was applied to find the variants at the loci.
  
  
  RESULTS
  We identified two candidate loci in each family and homozygous truncating mutations p.R611X in TAF4B in family 1 and p.K507Sfs*3 in ZMYND15 in family 2. We did not detect any mutations in these genes in a cohort of 45 azoospermic and 15 oligozoospermic men. Expression studies for ZMYND15 showed that the highest expression was in the testis.
  
  
  CONCLUSIONS
  Both genes are known to have roles in spermatogenesis in mice but neither has been studied in humans. To our knowledge, they are the first genes identified for recessive idiopathic spermatogenic failure in men. Assuming that recessive genes for isolated azoospermia are as numerous in men as in mice, each gene is possibly responsible for only a small fraction of all cases.
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey.
authors.forename: Özgecan
authors.initials: Ö
authors.lastname: Ayhan
authors.forename: Mahmut
authors.initials: M
authors.lastname: Balkan
authors.forename: Ayse
authors.initials: A
authors.lastname: Guven
authors.forename: Renin
authors.initials: R
authors.lastname: Hazan
authors.forename: Murat
authors.initials: M
authors.lastname: Atar
authors.forename: Atalay
authors.initials: A
authors.lastname: Tok
authors.forename: Aslıhan
authors.initials: A
authors.lastname: Tolun
mesh_terms: D000818:Animals; D053713:Azoospermia / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics*; D035362:Transcription Factor TFIID / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C101881:TAF4B protein, human; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID
keywords: Azoospermia; Male Infertility; SPAG7; TAF4B; Zmynd15