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A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella
INTRODUCTION: A previous study suggested that loss of CFAP47 function is involved in multiple morphological abnormalities of the sperm flagella (MMAF) in humans and mice. However, the comprehensive role of CFAP47 in spermatogenesis is largely unknown. METHODS: Whole-exome sequencing (WES) was conduc...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326514/ https://www.ncbi.nlm.nih.gov/pubmed/37424856 http://dx.doi.org/10.3389/fendo.2023.1155639 |
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author | Liu, Mohan Dai, Siyu Zhang, Jiying Yang, Yihong Shen, Ying Liu, Hongqian Yang, Yanting Jiang, Chuan Tian, Erpo |
author_facet | Liu, Mohan Dai, Siyu Zhang, Jiying Yang, Yihong Shen, Ying Liu, Hongqian Yang, Yanting Jiang, Chuan Tian, Erpo |
author_sort | Liu, Mohan |
collection | PubMed |
description | INTRODUCTION: A previous study suggested that loss of CFAP47 function is involved in multiple morphological abnormalities of the sperm flagella (MMAF) in humans and mice. However, the comprehensive role of CFAP47 in spermatogenesis is largely unknown. METHODS: Whole-exome sequencing (WES) was conducted to identify pathogenic variant in two patients with MMAF. The functional effect of the identified mutations was investigated by immunofluorescence staining and western blotting. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with MMAF. RESULTS: In this study, we identified a novel missense mutation (c.1414G>A; p.V472M) in CFAP47 in two unrelated patients with oligoasthenoteratozoospermia. Intriguingly, in addition to the MMAF phenotype very analogous to the previous report, the two patients notably presented abnormal morphology of sperm heads, the sperm mitochondrial sheath was obviously disorganized, and the sperm annulus were almost defective. Further functional experiments confirmed that the expression of CFAP47 was markedly reduced in the spermatozoa of the patients. Mechanism analysis suggested that CFAP47 might regulate the expression of CFAP65, CFAP69 and SEPTIN4 through their physical interactions and thus modulating sperm morphogenesis. CONCLUSION: we revealed a novel mutation in CFAP47 and further expanded the phenotype and mutation spectrum of CFAP47, as well as the potential mechanism of CFAP47 manipulating spermatogenesis, finally providing important guidance for genetic counseling and targeted treatment for CFAP47 mutation-related male infertility. |
format | Online Article Text |
id | pubmed-10326514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103265142023-07-08 A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella Liu, Mohan Dai, Siyu Zhang, Jiying Yang, Yihong Shen, Ying Liu, Hongqian Yang, Yanting Jiang, Chuan Tian, Erpo Front Endocrinol (Lausanne) Endocrinology INTRODUCTION: A previous study suggested that loss of CFAP47 function is involved in multiple morphological abnormalities of the sperm flagella (MMAF) in humans and mice. However, the comprehensive role of CFAP47 in spermatogenesis is largely unknown. METHODS: Whole-exome sequencing (WES) was conducted to identify pathogenic variant in two patients with MMAF. The functional effect of the identified mutations was investigated by immunofluorescence staining and western blotting. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with MMAF. RESULTS: In this study, we identified a novel missense mutation (c.1414G>A; p.V472M) in CFAP47 in two unrelated patients with oligoasthenoteratozoospermia. Intriguingly, in addition to the MMAF phenotype very analogous to the previous report, the two patients notably presented abnormal morphology of sperm heads, the sperm mitochondrial sheath was obviously disorganized, and the sperm annulus were almost defective. Further functional experiments confirmed that the expression of CFAP47 was markedly reduced in the spermatozoa of the patients. Mechanism analysis suggested that CFAP47 might regulate the expression of CFAP65, CFAP69 and SEPTIN4 through their physical interactions and thus modulating sperm morphogenesis. CONCLUSION: we revealed a novel mutation in CFAP47 and further expanded the phenotype and mutation spectrum of CFAP47, as well as the potential mechanism of CFAP47 manipulating spermatogenesis, finally providing important guidance for genetic counseling and targeted treatment for CFAP47 mutation-related male infertility. Frontiers Media S.A. 2023-06-23 /pmc/articles/PMC10326514/ /pubmed/37424856 http://dx.doi.org/10.3389/fendo.2023.1155639 Text en Copyright © 2023 Liu, Dai, Zhang, Yang, Shen, Liu, Yang, Jiang and Tian https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Liu, Mohan Dai, Siyu Zhang, Jiying Yang, Yihong Shen, Ying Liu, Hongqian Yang, Yanting Jiang, Chuan Tian, Erpo A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella |
title | A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella |
title_full | A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella |
title_fullStr | A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella |
title_full_unstemmed | A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella |
title_short | A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella |
title_sort | novel mutation in cfap47 causes male infertility due to multiple morphological abnormalities of the sperm flagella |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326514/ https://www.ncbi.nlm.nih.gov/pubmed/37424856 http://dx.doi.org/10.3389/fendo.2023.1155639 |
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