A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms
Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm a...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2022-01-01
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| Series: | Asian Journal of Andrology |
| Subjects: | |
| Online Access: | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2022;volume=24;issue=3;spage=255;epage=259;aulast=Zubair |
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| author | Muhammad Zubair Ranjha Khan Ao Ma Uzma Hameed Mazhar Khan Tanveer Abbas Riaz Ahmad Jian-Teng Zhou Wasim Shah Ansar Hussain Nisar Ahmed Ihsan Khan Khalid Khan Yuan-Wei Zhang Huan Zhang Li-Min Wu Qing-Hua Shi |
| author_facet | Muhammad Zubair Ranjha Khan Ao Ma Uzma Hameed Mazhar Khan Tanveer Abbas Riaz Ahmad Jian-Teng Zhou Wasim Shah Ansar Hussain Nisar Ahmed Ihsan Khan Khalid Khan Yuan-Wei Zhang Huan Zhang Li-Min Wu Qing-Hua Shi |
| author_sort | Muhammad Zubair |
| collection | DOAJ |
| description | Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia. |
| first_indexed | 2024-12-12T11:42:21Z |
| format | Article |
| id | doaj.art-49b2f11af3484562aa0d765abcf0a085 |
| institution | Directory Open Access Journal |
| issn | 1008-682X 1745-7262 |
| language | English |
| last_indexed | 2024-12-12T11:42:21Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Asian Journal of Andrology |
| spelling | doaj.art-49b2f11af3484562aa0d765abcf0a0852022-12-22T00:25:30ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X1745-72622022-01-0124325525910.4103/aja2021122A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein armsMuhammad ZubairRanjha KhanAo MaUzma HameedMazhar KhanTanveer AbbasRiaz AhmadJian-Teng ZhouWasim ShahAnsar HussainNisar AhmedIhsan KhanKhalid KhanYuan-Wei ZhangHuan ZhangLi-Min WuQing-Hua ShiAsthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.http://www.ajandrology.com/article.asp?issn=1008-682X;year=2022;volume=24;issue=3;spage=255;epage=259;aulast=Zubairasthenoteratozoospermia; ccdc103; dynein arms; male infertility |
| spellingShingle | Muhammad Zubair Ranjha Khan Ao Ma Uzma Hameed Mazhar Khan Tanveer Abbas Riaz Ahmad Jian-Teng Zhou Wasim Shah Ansar Hussain Nisar Ahmed Ihsan Khan Khalid Khan Yuan-Wei Zhang Huan Zhang Li-Min Wu Qing-Hua Shi A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms Asian Journal of Andrology asthenoteratozoospermia; ccdc103; dynein arms; male infertility |
| title | A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms |
| title_full | A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms |
| title_fullStr | A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms |
| title_full_unstemmed | A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms |
| title_short | A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms |
| title_sort | recurrent homozygous missense mutation in ccdc103 causes asthenoteratozoospermia due to disorganized dynein arms |
| topic | asthenoteratozoospermia; ccdc103; dynein arms; male infertility |
| url | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2022;volume=24;issue=3;spage=255;epage=259;aulast=Zubair |
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