A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family

Article In Press

0
0

Authors:

Ying Ma, Ph.D.a,b, Ning Xie, M.D.c, Dingxiong Xie, M.D.d,e, Litao Sun, Ph.D.f, Shuyan Li, Ph.D.g, Peiqiang Li, Ph.D.a, Yi Li, Ph.D.a,h, Jin Li, Ph.D.f, Zhilong Dong, Ph.D.i, Xiaodong Xie, Ph.D.a,∗

Abstract:

Objective

To identify the genetic causes of male infertility characterized by teratozoospermia.

Design

Genetic studies.

Setting

Medical university.

Patient(s)

Two infertile brothers with teratozoospermia in a consanguineous Chinese family, another 124 sporadic infertile male patients presenting with teratozoospermia, and 200 male controls with normal fertility.

Invention(s)

None.

Main Outcome Measure(s)

Whole exome sequencing and genotype analysis to identify the potential pathogenic mutation, Sanger sequencing to validate the mutation in family members, in silico structural modeling to predict the functional consequences of mutation, and targeted next-generation sequencing to validate the mutation in sporadic cases.

Result(s)

A novel homozygous nonsynonymous mutation (C1991T, p.G664D) in FBXO43 (F-box only protein 43) was observed in two brothers from a consanguineous Chinese family. The mutation was segregated with the disease phenotype and was predicted to be a disease causing protein by SIFT, PolyPhen-2, and Mutation Taster. An in silico mutant FBXO43 model predicts that the mutation p.G664D causes shortening of two β-sheets, an additional α-helix, and change in loops, which may result in loss of function of the protein. The homozygous mutation of FBXO43 was absent in the 1000 Genomes Project (1000 G) and the Exome Aggregation Consortium (ExAC) databases. Subsequent mutation screening of FBXO43 in a cohort of 124 cases identified four additional cases with heterozygous FBXO43 mutations. No mutations were found in FBXO43 in 200 fertile controls.

Conclusion(s)

The mutation in FBXO43 is a causative factor of male infertility and teratozoospermia.


Read the full text here.


Go to the profile of Fertility and Sterility

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

No comments yet.