Faculty Collaboration Database

Novel IFT140 variants cause spermatogenic dysfunction in humans. Mol Genet Genomic Med 2019 Sep;7(9):e920

Date

08/10/2019

Pubmed ID

31397098

Pubmed Central ID

PMC6732298

DOI

10.1002/mgg3.920

Scopus ID

2-s2.0-85070300940 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

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.

Author List

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

Author

Ling Mei MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Amino Acid Substitution
Carrier Proteins
Exons
Humans
Infertility, Male
Male
Mutation
Mutation, Missense