Identification of a homozygous GFPT2 variant in a family with asthenozoospermia.
PURPOSEAsthenozoospermia (ASZ) is a condition characterized by reduced sperm motility in semen affecting approximately 19% of infertile men. Major risk factors, particularly gene mutations, still remain unknown. The main aim of the present study was to identify novel genes and mutations that may influence human sperm motility.
METHODSWhole-exome sequencing (WES) was performed on a large pedigree of infertile men (n = 5) followed by bioinformatics analyses. Candidate pathogenic variants were screened in a control cohort of 400 ancestry-matched Iranian fertile men, 30 unrelated men with idiopathic ASZ, and public databases.
RESULTSA rare mutation in GFPT2 gene (c.1097G > A; p.Arg366Gln) located in the SIS 1 domain was segregated with the phenotype and was consistent with autosomal recessive inheritance. The in silico analyses revealed that the mutation might affect the function of SIS 1 domain and abolish its carbohydrate-binding ability.
CONCLUSIONHomozygosity of the GFPT2 p.Arg366Gln mutation was associated with increased levels of reactive oxygen species (ROS) in spermatozoa and decreased sperm motility.
Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran.,
Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran. Electronic address: firstname.lastname@example.org.,
Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.,
Human Developmental Genetics, Institute Pasteur, Paris, France.
Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address: email@example.com.
MeSHAmino Acid Sequence
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
Reactive Oxygen Species
Whole Exome Sequencing
Pub Type(s)Journal Article