Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia

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• 作者：Esther Maor-Sagie ; Yuval Cinnamon…
• 关键词：Meiosis ; Azoospermia ; Maturation arrest ; Exome sequencing
• 刊名：Journal of Assisted Reproduction and Genetics
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：32
• 期：6
• 页码：887-891
• 全文大小：732 KB
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• 作者单位：Esther Maor-Sagie (1) (2)
  Yuval Cinnamon (1) (4)
  Barak Yaacov (1)
  Avraham Shaag (1)
  Hannoch Goldsmidt (3)
  Shamir Zenvirt (1)
  Neri Laufer (2)
  Carmelit Richler (1)
  Ayala Frumkin (1)
  
  1. The Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
  2. Department of Obstetrics and Gynecology, Hadassah Ein-Karem, Hebrew University Medical Center, Jerusalem, Israel
  4. Institute of Animal Science, ARO, The Volcani Center, PO Box 6, Bet Dagan, 50250, Israel
  3. Department of Pathology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Gynecology
  Developmental Biology
  Human Genetics
  
• 出版者：Springer Netherlands
• ISSN：1573-7330

文摘

Purpose 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. Conclusion 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.