title: A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes.
abstract: Up to 1% of all men experience azoospermia, a condition of complete absence of sperm in the semen. The mechanisms and genes involved in spermatogenesis are mainly studied in model organisms, and their relevance to humans is unclear because human genetic studies are very scarce. Our objective was to uncover novel human mutations and genes causing azoospermia due to testicular meiotic maturation arrest.
  
  
  
  Affected and unaffected siblings from three families were subjected to whole-exome or whole-genome sequencing, followed by comprehensive bioinformatics analyses to identify mutations suspected to cause azoospermia. These likely mutations were further screened in azoospermic and normozoospermic men and in men proven to be fertile, as well as in a reference database of local populations.
  
  
  
  We identified three novel likely causative mutations of azoospermia in three genes: MEIOB, TEX14, and DNAH6. These genes are associated with different meiotic processes: meiotic crossovers, daughter cell abscission, and possibly rapid prophase movements.
  
  
  
  The genes and pathways we identified are fundamental for delineating common causes of azoospermia originating in mutations affecting diverse meiotic processes and have great potential for accelerating approaches to diagnose, treat, and prevent infertility.Genet Med advance online publication 16 February 2017.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Moran
authors.identifier: 0000-0002-2179-0799
authors.initials: M
authors.lastname: Gershoni
authors.affiliation: Racine IVF Unit and Male Fertility Clinic and Sperm Bank, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Hauser
authors.affiliation: Racine IVF Unit and Male Fertility Clinic and Sperm Bank, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Leah
authors.initials: L
authors.lastname: Yogev
authors.affiliation: Racine IVF Unit and Male Fertility Clinic and Sperm Bank, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ofer
authors.identifier: 0000-0002-7003-3532
authors.initials: O
authors.lastname: Lehavi
authors.affiliation: Racine IVF Unit and Male Fertility Clinic and Sperm Bank, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Foad
authors.initials: F
authors.lastname: Azem
authors.affiliation: Racine IVF Unit and Male Fertility Clinic and Sperm Bank, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Yavetz
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Pietrokovski
authors.affiliation: Racine IVF Unit and Male Fertility Clinic and Sperm Bank, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sandra E
authors.identifier: 0000-0003-0245-9694
authors.initials: SE
authors.lastname: Kleiman
mesh_terms: D000595:Amino Acid Sequence; D053713:Azoospermia / Q000175:diagnosis* / Q000235:genetics*; D015415:Biomarkers; D001706:Biopsy; D016022:Case-Control Studies; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D004398:Dyneins / Q000235:genetics; D005190:Family; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009154:Mutation; D010375:Pedigree; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C587161:MEIOB protein, human; D004398:Dyneins