Journal article

Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility

Chunyu Liu, Chaofeng Tu, Lingbo Wang, Huan Wu, Brendan J Houston, Francesco K Mastrorosa, Wen Zhang, Ying Shen, Jiaxiong Wang, Shixiong Tian, Lanlan Meng, Jiangshan Cong, Shenmin Yang, Yiwen Jiang, Shuyan Tang, Yuyan Zeng, Mingrong Lv, Ge Lin, Jinsong Li, Hexige Saiyin Show all

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2021

Abstract

Asthenoteratozoospermia characterized by multiple morphological abnormalities of the flagella (MMAF) has been identified as a sub-type of male infertility. Recent progress has identified several MMAF-associated genes with an autosomal recessive inheritance in human affected individuals, but the etiology in approximately 40% of affected individuals remains unknown. Here, we conducted whole-exome sequencing (WES) and identified hemizygous missense variants in the X-linked CFAP47 in three unrelated Chinese individuals with MMAF. These three CFAP47 variants were absent in human control population genome databases and were predicted to be deleterious by multiple bioinformatic tools. CFAP47 encode..

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Grants

Awarded by National Natural Science Foundation of China


Awarded by Shanghai Municipal Science and Technology Major Project


Awarded by China Postdoctoral Science Foundation


Awarded by State Key Laboratory of Reproductive Medicine


Awarded by Science and Technology Major Project of Inner Mongolia Autonomous Region of China


Awarded by key grant of prevention and treatment of birth defect from Hunan Province


Awarded by National Key Research and Developmental Program of China


Awarded by Shanghai Municipal Commission for Science and Technology


Awarded by Foundation of the Department of Science and Technology of Anhui Province


Awarded by Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences


Awarded by National Key Research and Development Program of China


Awarded by Agence Nationale pour la Recherche


Awarded by Innovative Research Team of High-level Local Universities in Shanghai


Awarded by National Health and Medical Research Council


Awarded by Investigator Award in Science from TheWellcome Trust


Funding Acknowledgements

We would like to thank the families for participating and supporting this study. We also thank the Center of Cryo-electron Microscopy at Zhejiang University for technical support. This work was supported by National Natural Science Foundation of China (31625015, 31521003, 81971447, 81971441, 81871216, 81901541, and 81601340), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), China Postdoctoral Science Foundation (2020TQ0072 and 2019M662786), State Key Laboratory of Reproductive Medicine (SKLRM-K202002), Science and Technology Major Project of Inner Mongolia Autonomous Region of China (zdzx2018065), the key grant of prevention and treatment of birth defect from Hunan Province (2019SK1012), the National Key Research and Developmental Program of China (2018YFC1004900), Shanghai Municipal Commission for Science and Technology (19QA1407500 and 18ZR1432300), Foundation of the Department of Science and Technology of Anhui Province (2017070802D150), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT310002), the National Key Research and Development Program of China (2016YFC1000204), the Agence Nationale pour la Recherche (FLAGEL-OME ANR-19-CE17-0014), and Innovative Research Team of High-level Local Universities in Shanghai (SSMUZLCX20180500). The sequencing and analysis of Australian patients was supported in part by a grant from the National Health and Medical Research Council (APP1120356) and an Investigator Award in Science from TheWellcome Trust (209451). We acknowledge the ongoing support of Professor Rob McLachlan and the Monash IVF Group of infertility clinics in Australia for their role in patient recruitment and treatment.