A hemizygous loss-of-function variant in BCORL1 is associated with male infertility and oligoasthenoteratozoospermia
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..
Oligoasthenoteratozoospermia (OAT) is a common type of male infertility; however, its genetic causes remain largely unknown. Some of the genetic determinants of OAT are gene defects affecting spermatogenesis. BCORL1 (BCL6 corepressor like 1) is a transcriptional corepressor that exhibits the OAT phenotype in a knockout mouse model. A hemizygous missense variant of BCORL1 (c.2615T > G:p.Val872Gly) was reported in an infertile male patient with non-obstructive azoospermia (NOA). Nevertheless, the correlation between BCORL1 variants and OAT in humans remains unknown. In this study, we used whole-exome sequencing to identify a novel hemizygous nonsense variant of BCORL1 (c.1564G > T:p.Glu522*) in a male patient with OAT from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Further population screening identified four BCORL1 missense variants in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%), but no pathogenic BCORL1 variants among 362 fertile subjects. In conclusion, our findings indicate that BCORL1 is a potential candidate gene in the pathogenesis of OAT and NOA, expanded its disease spectrum and suggested that BCORL1 may play a role in spermatogenesis by interacting with SKP1.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Clinical genetics - (2024) vom: 11. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Luo, Chen [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
BCORL1 |
|---|
| Anmerkungen: |
Date Revised 11.02.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1111/cge.14500 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368325520 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368325520 | ||
| 003 | DE-627 | ||
| 005 | 20240212232235.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240212s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/cge.14500 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1289.xml |
| 035 | |a (DE-627)NLM368325520 | ||
| 035 | |a (NLM)38342987 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Luo, Chen |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A hemizygous loss-of-function variant in BCORL1 is associated with male infertility and oligoasthenoteratozoospermia |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 11.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | ||
| 520 | |a Oligoasthenoteratozoospermia (OAT) is a common type of male infertility; however, its genetic causes remain largely unknown. Some of the genetic determinants of OAT are gene defects affecting spermatogenesis. BCORL1 (BCL6 corepressor like 1) is a transcriptional corepressor that exhibits the OAT phenotype in a knockout mouse model. A hemizygous missense variant of BCORL1 (c.2615T > G:p.Val872Gly) was reported in an infertile male patient with non-obstructive azoospermia (NOA). Nevertheless, the correlation between BCORL1 variants and OAT in humans remains unknown. In this study, we used whole-exome sequencing to identify a novel hemizygous nonsense variant of BCORL1 (c.1564G > T:p.Glu522*) in a male patient with OAT from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Further population screening identified four BCORL1 missense variants in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%), but no pathogenic BCORL1 variants among 362 fertile subjects. In conclusion, our findings indicate that BCORL1 is a potential candidate gene in the pathogenesis of OAT and NOA, expanded its disease spectrum and suggested that BCORL1 may play a role in spermatogenesis by interacting with SKP1 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BCORL1 | |
| 650 | 4 | |a BCORL1-SKP1 interaction | |
| 650 | 4 | |a male infertility | |
| 650 | 4 | |a oligoasthenoteratozoospermia | |
| 650 | 4 | |a spermatogenesis | |
| 700 | 1 | |a Chen, Zixu |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Lanlan |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a He, Wenbin |e verfasserin |4 aut | |
| 700 | 1 | |a Tu, Chaofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Guang-Xiu |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ge |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Yue-Qiu |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Tong-Yao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical genetics |d 1971 |g (2024) vom: 11. Feb. |w (DE-627)NLM00004914X |x 1399-0004 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:11 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/cge.14500 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 11 |c 02 | ||