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...

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Bibliographic Details
Published in:Asian journal of andrology 2022-05, Vol.24 (3), p.255-259
Main Authors: Zubair, Muhammad, Khan, Ranjha, Ma, Ao, Hameed, Uzma, Khan, Mazhar, Abbas, Tanveer, Ahmad, Riaz, Zhou, Jian-Teng, Shah, Wasim, Hussain, Ansar, Ahmed, Nisar, Khan, Ihsan, Khan, Khalid, Zhang, Yuan-Wei, Zhang, Huan, Wu, Li-Min, Shi, Qing-Hua
Format: Article
Language:English
Subjects:
asthenoteratozoospermia
ccdc103
dynein arms
male infertility
Asthenozoospermia - genetics
Asthenozoospermia - pathology
Dynein
Dyneins - genetics
Genetic aspects
Genotype & phenotype
Homozygote
Humans
Male
Microtubule-Associated Proteins
Mutation
Mutation, Missense
Original
Sperm
Sperm Tail - metabolism
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Summary: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.
ISSN:1008-682X
1745-7262
DOI:10.4103/aja2021122