A recurrent homozygous missense mutation in <i>CCDC103</i> causes asthenoteratozoospermia due to disorganized dynein arms.

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

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A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms.

Author: Muhammad ZUBAIR ¹ ; Ranjha KHAN ¹ ; Ao MA ¹ ; Uzma HAMEED ² ; Mazhar KHAN ¹ ; Tanveer ABBAS ¹ ; Riaz AHMAD ³ ; Jian-Teng ZHOU ¹ ; Wasim SHAH ¹ ; Ansar HUSSAIN ¹ ; Nisar AHMED ¹ ; Ihsan KHAN ¹ ; Khalid KHAN ¹ ; Yuan-Wei ZHANG ¹ ; Huan ZHANG ¹ ; Li-Min WU ¹ ; Qing-Hua SHI ¹
Author Information

1. The First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei 230027, China.
2. Institute of Industrial Biotechnology, Government College University, Lahore 54000, Pakistan.
3. Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Publication Type:Journal Article
Keywords: CCDC103; asthenoteratozoospermia; dynein arms; male infertility
MeSH: Asthenozoospermia/pathology*; Dyneins/genetics*; Homozygote; Humans; Male; Microtubule-Associated Proteins; Mutation; Mutation, Missense; Sperm Tail/metabolism*
From: Asian Journal of Andrology 2022;24(3):255-259
CountryChina
Language:English
Abstract: 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.