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Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families
Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577262/ https://www.ncbi.nlm.nih.gov/pubmed/34100391 http://dx.doi.org/10.4103/aja.aja_26_21 |
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author | Khan, Ihsan Shah, Basit Dil, Sobia Ullah, Nadeem Zhou, Jian-Teng Zhao, Da-Ren Zhang, Yuan-Wei Jiang, Xiao-Hua Khan, Ranjha Khan, Asad Ali, Haider Zubair, Muhammad Shah, Wasim Zhang, Huan Shi, Qing-Hua |
author_facet | Khan, Ihsan Shah, Basit Dil, Sobia Ullah, Nadeem Zhou, Jian-Teng Zhao, Da-Ren Zhang, Yuan-Wei Jiang, Xiao-Hua Khan, Ranjha Khan, Asad Ali, Haider Zubair, Muhammad Shah, Wasim Zhang, Huan Shi, Qing-Hua |
author_sort | Khan, Ihsan |
collection | PubMed |
description | Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins (CFAPs; e.g., CFAP43, CFAP44, CFAP65, CFAP69, CFAP70, and CFAP251) responsible for the MMAF phenotype in infertile men from different ethnic groups. However, none of them have been identified in infertile Pakistani males with MMAF. In the current study, two Pakistani families with MMAF patients were recruited. Whole-exome sequencing (WES) of patients and their parents was performed. WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families (Family 1: ENST00000357060.3, p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state; Family 2: ENST00000357060.3, p.Thr526Serfs*43 in a homozygous state). Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype. Semiquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to detect the effect of the mutation on mRNA of the affected gene. Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients. To the best of our knowledge, this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype. This study will help researchers and clinicians to understand the genetic etiology of MMAF better. |
format | Online Article Text |
id | pubmed-8577262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-85772622021-11-10 Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families Khan, Ihsan Shah, Basit Dil, Sobia Ullah, Nadeem Zhou, Jian-Teng Zhao, Da-Ren Zhang, Yuan-Wei Jiang, Xiao-Hua Khan, Ranjha Khan, Asad Ali, Haider Zubair, Muhammad Shah, Wasim Zhang, Huan Shi, Qing-Hua Asian J Androl Original Article Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins (CFAPs; e.g., CFAP43, CFAP44, CFAP65, CFAP69, CFAP70, and CFAP251) responsible for the MMAF phenotype in infertile men from different ethnic groups. However, none of them have been identified in infertile Pakistani males with MMAF. In the current study, two Pakistani families with MMAF patients were recruited. Whole-exome sequencing (WES) of patients and their parents was performed. WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families (Family 1: ENST00000357060.3, p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state; Family 2: ENST00000357060.3, p.Thr526Serfs*43 in a homozygous state). Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype. Semiquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to detect the effect of the mutation on mRNA of the affected gene. Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients. To the best of our knowledge, this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype. This study will help researchers and clinicians to understand the genetic etiology of MMAF better. Wolters Kluwer - Medknow 2021-05-28 /pmc/articles/PMC8577262/ /pubmed/34100391 http://dx.doi.org/10.4103/aja.aja_26_21 Text en Copyright: © The Author(s)(2021) https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Khan, Ihsan Shah, Basit Dil, Sobia Ullah, Nadeem Zhou, Jian-Teng Zhao, Da-Ren Zhang, Yuan-Wei Jiang, Xiao-Hua Khan, Ranjha Khan, Asad Ali, Haider Zubair, Muhammad Shah, Wasim Zhang, Huan Shi, Qing-Hua Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families |
title | Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families |
title_full | Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families |
title_fullStr | Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families |
title_full_unstemmed | Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families |
title_short | Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families |
title_sort | novel biallelic loss-of-function mutations in cfap43 cause multiple morphological abnormalities of the sperm flagellum in pakistani families |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577262/ https://www.ncbi.nlm.nih.gov/pubmed/34100391 http://dx.doi.org/10.4103/aja.aja_26_21 |
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