• PMID: 31397098
• Gene Name: IFT140
• Condition: Spermatogenic dysfunction, Oligozoospermia, asthenozoospermia, teratozoospermia
• Association: Associated
• Mutation: Exon16: c.1837G > A: p.Asp613Asn and exon31: c.4247G > A: p.Ser1416Asn
• Population size: 4
• Population details: 1 fertile man presented with severe oligozoospermia, asthenozoospermia, and teratozoospermia (OAT) without other physical abnormality, 3 family members
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

Novel IFT140 variants cause spermatogenic dysfunction in humans

Wang X, Sha YW, Wang WT, Cui YQ, Chen J, Yan W, Hou XT, Mei LB, Yu CC, Wang J.

BACKGROUND: The intraflagellar transport protein 140 homolog (IFT140) is involved in the process of intraflagellar transport (IFT), a process that is essential for the formation and maintenance of most eukaryotic cilia and flagella. Variants IFT140 have been reported to account for ciliopathy but association with male fertility has never been described in humans. Here we report the identification of two novel variants of IFT140 which caused spermatogenic dysfunction and male infertility. METHODS: Whole-exome sequencing was performed in a 27-year-old infertile man presented with severe oligozoospermia, asthenozoospermia, and teratozoospermia (OAT) without other physical abnormality. Sanger sequencing was used to verify gene variants in the patient, his healthy brother, and their parents. Morphology and protein expression in the patient's sperm were examined by transmission electron microscopy (TEM) and immunofluorescence staining. Function of gene variants was predicted by online databases. RESULTS: Compound heterozygous variants of IFT140: exon16: c.1837G > A: p.Asp613Asn and exon31: c.4247G > A: p.Ser1416Asn were identified in the patient, both of which showed autosomal recessive inheritance in his family, and had extremely low allele frequency in the population. Morphological abnormalities of the head, nucleus, and tails and the absence of IFT140 from the neck and mid-piece of the patient's spermatozoa were observed. Mutation Taster database predicted a high probability of damage-causing by both variations. CONCLUSION: This study for the first time reported IFT140 variants that cause infertility in humans. CI - © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. FAU - Wang, Xiong AU - Wang X AD - Department of Reproductive Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, China. FAU - Sha, Yan-Wei AU - Sha YW AD - Department of Reproductive Medicine, Xiamen Maternal and Child Care Hospital, Xiamen, Fujian, China. FAU - Wang, Wen-Ting AU - Wang WT AD - Central Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. FAU - Cui, Yuan-Qing AU - Cui YQ AD - Department of Reproductive Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, China. FAU - Chen, Jie AU - Chen J AD - Department of Reproductive Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, China. FAU - Yan, Wei AU - Yan W AD - Department of Reproductive Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, China. FAU - Hou, Xiao-Tao AU - Hou XT AD - Pathology Department, Guangzhou KingMed Center for Clinical Laboratory Co. Ltd, Guangzhou, Guangdong, China. FAU - Mei, Li-Bin AU - Mei LB AD - Department of Reproductive Medicine, Xiamen Maternal and Child Care Hospital, Xiamen, Fujian, China. FAU - Yu, Cui-Cui AU - Yu CC AD - Department of Anesthesiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.