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Article: A pathogenic DMC1 frameshift mutation causes nonobstructive azoospermia but not primary ovarian insufficiency in humans

TitleA pathogenic DMC1 frameshift mutation causes nonobstructive azoospermia but not primary ovarian insufficiency in humans
Authors
KeywordsNonobstructive azoospermia
Diminished ovarian reserve
Whole-exome sequencing
DNA meiotic Recombinase 1 (DMC1)
Homozygous frameshift mutation
Spermatogenesis
Oogenesis
Mouse study
Human study
Sexual dimorphism
Issue Date2021
PublisherOxford University Press. The Journal's web site is located at http://molehr.oxfordjournals.org/
Citation
Molecular Human Reproduction, 2021, v. 27 n. 9, article no. gaab058 How to Cite?
AbstractNonobstructive azoospermia (NOA) and diminished ovarian reserve (DOR) are two disorders that can lead to infertility in males and females. Genetic factors have been identified to contribute to NOA and DOR. However, the same genetic factor that can cause both NOA and DOR remains largely unknown. To explore the candidate pathogenic gene that causes both NOA and DOR, we conducted whole-exome sequencing (WES) in a non-consanguineous family with two daughters with DOR and a son with NOA. We detected one pathogenic frameshift variant (NM_007068:c.28delG, p. Glu10Asnfs*31) following a recessive inheritance mode in a meiosis gene DMC1 (DNA meiotic recombinase 1). Clinical analysis showed reduced antral follicle number in both daughters with DOR, but metaphase II oocytes could be retrieved from one of them. For the son with NOA, no spermatozoa were found after microsurgical testicular sperm extraction. A further homozygous Dmc1 knockout mice study demonstrated total failure of follicle development and spermatogenesis. These results revealed a discrepancy of DMC1 action between mice and humans. In humans, DMC1 is required for spermatogenesis but is dispensable for oogenesis, although the loss of function of this gene may lead to DOR. To our knowledge, this is the first report on the homozygous frameshift mutation as causative for both NOA and DOR and demonstrating that DMC1 is dispensable in human oogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/305932
ISSN
2023 Impact Factor: 3.6
2023 SCImago Journal Rankings: 1.201
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCao, D-
dc.contributor.authorShi, F-
dc.contributor.authorGuo, C-
dc.contributor.authorLiu, Y-
dc.contributor.authorLin, Z-
dc.contributor.authorZhang, J-
dc.contributor.authorLi, RHW-
dc.contributor.authorYao, Y-
dc.contributor.authorLiu, K-
dc.contributor.authorNg, EHY-
dc.contributor.authorYeung, WSB-
dc.contributor.authorWang, T-
dc.date.accessioned2021-10-20T10:16:24Z-
dc.date.available2021-10-20T10:16:24Z-
dc.date.issued2021-
dc.identifier.citationMolecular Human Reproduction, 2021, v. 27 n. 9, article no. gaab058-
dc.identifier.issn1360-9947-
dc.identifier.urihttp://hdl.handle.net/10722/305932-
dc.description.abstractNonobstructive azoospermia (NOA) and diminished ovarian reserve (DOR) are two disorders that can lead to infertility in males and females. Genetic factors have been identified to contribute to NOA and DOR. However, the same genetic factor that can cause both NOA and DOR remains largely unknown. To explore the candidate pathogenic gene that causes both NOA and DOR, we conducted whole-exome sequencing (WES) in a non-consanguineous family with two daughters with DOR and a son with NOA. We detected one pathogenic frameshift variant (NM_007068:c.28delG, p. Glu10Asnfs*31) following a recessive inheritance mode in a meiosis gene DMC1 (DNA meiotic recombinase 1). Clinical analysis showed reduced antral follicle number in both daughters with DOR, but metaphase II oocytes could be retrieved from one of them. For the son with NOA, no spermatozoa were found after microsurgical testicular sperm extraction. A further homozygous Dmc1 knockout mice study demonstrated total failure of follicle development and spermatogenesis. These results revealed a discrepancy of DMC1 action between mice and humans. In humans, DMC1 is required for spermatogenesis but is dispensable for oogenesis, although the loss of function of this gene may lead to DOR. To our knowledge, this is the first report on the homozygous frameshift mutation as causative for both NOA and DOR and demonstrating that DMC1 is dispensable in human oogenesis.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://molehr.oxfordjournals.org/-
dc.relation.ispartofMolecular Human Reproduction-
dc.subjectNonobstructive azoospermia-
dc.subjectDiminished ovarian reserve-
dc.subjectWhole-exome sequencing-
dc.subjectDNA meiotic Recombinase 1 (DMC1)-
dc.subjectHomozygous frameshift mutation-
dc.subjectSpermatogenesis-
dc.subjectOogenesis-
dc.subjectMouse study-
dc.subjectHuman study-
dc.subjectSexual dimorphism-
dc.titleA pathogenic DMC1 frameshift mutation causes nonobstructive azoospermia but not primary ovarian insufficiency in humans-
dc.typeArticle-
dc.identifier.emailLi, RHW: raymondli@hku.hk-
dc.identifier.emailLiu, K: kliugc@hku.hk-
dc.identifier.emailNg, EHY: nghye@hku.hk-
dc.identifier.emailYeung, WSB: wsbyeung@hku.hk-
dc.identifier.authorityLi, RHW=rp01649-
dc.identifier.authorityLiu, K=rp02475-
dc.identifier.authorityNg, EHY=rp00426-
dc.identifier.authorityYeung, WSB=rp00331-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/molehr/gaab058-
dc.identifier.pmid34515795-
dc.identifier.scopuseid_2-s2.0-85117406471-
dc.identifier.hkuros326639-
dc.identifier.volume27-
dc.identifier.issue9-
dc.identifier.spagearticle no. gaab058-
dc.identifier.epagearticle no. gaab058-
dc.identifier.isiWOS:000708764900004-
dc.publisher.placeUnited Kingdom-

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