A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes.
Genet Med
; 19(9): 998-1006, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28206990
ABSTRACT
PURPOSE:
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.METHODS:
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.RESULTS:
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.CONCLUSION:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
/
Azoospermia
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Estudos de Associação Genética
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Mutação
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article