2. Academic Validation
  3. A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family

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

  • Fertil Steril. 2019 May;111(5):909-917.e1. doi: 10.1016/j.fertnstert.2019.01.007.
Ying Ma 1,  Ning Xie 2,  Dingxiong Xie 3,  Litao Sun 4,  Shuyan Li 5,  Peiqiang Li 6,  Yi Li 7,  Jin Li 4,  Zhilong Dong 8,  Xiaodong Xie 9
Affiliations

Affiliations

  • 1 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Gansu Provincial Maternity and Child-care Hospital, Lanzhou, China.
  • 2 Lanzhou Municipal Center for Disease Control, Lanzhou, China.
  • 3 First People's Hospital of Lanzhou City, Lanzhou, China; Gansu Provincial Institute of Cardiovascular Diseases, Sun Yat-sen University, Guangdong, China.
  • 4 School of Public Health (Shenzhen), Sun Yat-sen University, Guangdong, China.
  • 5 College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, China.
  • 6 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
  • 7 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; School of Stomatology, Lanzhou University, Lanzhou, China.
  • 8 Lanzhou University Second Hospital, Lanzhou, China.
  • 9 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China. Electronic address: [email protected].
PMID: 30878252 DOI: 10.1016/j.fertnstert.2019.01.007
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.

Keywords

FBXO43; male infertility; mutation; teratozoospermia; whole exome sequencing.

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