
DOI . ORG {
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Title[redir]:
Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia | Journal of Assisted Reproduction and Genetics
Description:
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.
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Keywords {🔍}
article, pubmed, mutation, google, scholar, azoospermia, syce, nonobstructive, patients, synaptonemal, complex, central, cas, research, genet, privacy, cookies, content, analysis, data, journal, maorsagie, information, publish, search, genetics, esther, cinnamon, exome, sequencing, access, gene, hebrew, university, hadassah, author, center, israel, essential, site, log, deleterious, april, yuval, yaacov, molecular, family, genetic, samples, testicular,
Topics {✒️}
month download article/chapter article maor-sagie anti-syce1 antibody revealed central element proteins esther maor-sagie indicating maturation arrest infertility services reported full article pdf present report underscores autosomal-recessive form privacy choices/manage cookies jacques roboh department splice site mutation splice-acceptor mutation synaptonemal complex protein mutant mouse model premature ovarian failure synaptonemal complex proteins joint research fund chromosome azoospermia factors functional analysis reveals european economic area neri laufer premature stop codon meiotic genes underlying clin endocrinol metab excellent technical assistance conditions privacy policy syce1 gene exome sequencing autosomal-recessive national survey data patients’ testicular tissue accepting optional cookies article journal combining homozygosity mapping hum mol genet journal finder publish main content log hadassah ein-karem author correspondence article log yuval cinnamon hebrew university synaptonemal complex article cite check access instant access genetic research exome analysis
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headline:Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia
description:To determine the molecular basis of familial, autosomal-recessive, non-obstructive azoospermia in a consanguineous Iranian Jewish family. 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. 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. 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.
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Meiosis
Azoospermia
Maturation arrest
Exome sequencing
Gynecology
Reproductive Medicine
Human Genetics
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headline:Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia
description:To determine the molecular basis of familial, autosomal-recessive, non-obstructive azoospermia in a consanguineous Iranian Jewish family. 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. 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. 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.
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Meiosis
Azoospermia
Maturation arrest
Exome sequencing
Gynecology
Reproductive Medicine
Human Genetics
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