title: Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia.
abstract: OBJECTIVE
  To determine the molecular basis of familial, autosomal-recessive, non-obstructive azoospermia in a consanguineous Iranian Jewish family.
  
  
  METHODS
  We investigated the genetic cause of non-obstructive azoospermia in two affected siblings from a consanguineous family. Homozygosity mapping in the DNA samples of the patients and their normospermic brother was followed by exome analysis of one of the patients. Other family members were genotyped for the mutation by Sanger sequencing. The mutation effect was demonstrated by immunostaining of the patients' testicular tissue.
  
  
  RESULTS
  The two patients were homozygous for a splice site mutation in SYCE1 which resulted in retention of intron three in the cDNA and premature stop codon. SYCE1 encodes a Synaptonemal Complex protein which plays an essential role during meiosis. Immunostaining of patient's testicular tissue with anti-Syce1 antibody revealed an undetectable level of Syce1. Histological examination of the patients' tissue disclosed immature-stages spermatocytes without mature forms, indicating maturation arrest.
  
  
  CONCLUSIONS
  The significance of most synaptonemal complex proteins was previously demonstrated in a mutant mouse model. The present report underscores the importance of synaptonemal complex proteins in spermatogenenesis in humans. Our new approach, combining homozygosity mapping and exome sequencing, resulted in one of the first reports of an autosomal-recessive form of NOA.
authors.affiliation: The Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel, Estigal02@yahoo.com.
authors.forename: Esther
authors.initials: E
authors.lastname: Maor-Sagie
authors.forename: Yuval
authors.initials: Y
authors.lastname: Cinnamon
authors.forename: Barak
authors.initials: B
authors.lastname: Yaacov
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.forename: Hannoch
authors.initials: H
authors.lastname: Goldsmidt
authors.forename: Shamir
authors.initials: S
authors.lastname: Zenvirt
authors.forename: Neri
authors.initials: N
authors.lastname: Laufer
authors.forename: Carmelit
authors.initials: C
authors.lastname: Richler
authors.forename: Ayala
authors.initials: A
authors.lastname: Frumkin
mesh_terms: D053713:Azoospermia / Q000235:genetics*; D018389:Codon, Nonsense; D003241:Consanguinity; D004268:DNA-Binding Proteins; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D022821:RNA Splice Sites; C489753:SYCP1 protein, human