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Identification of a homozygous GFPT2 variant in a family with asthenozoospermia.

Abstract

PURPOSE

Asthenozoospermia (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.

METHODS

Whole-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.

RESULTS

A 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.

CONCLUSION

Homozygosity of the GFPT2 p.Arg366Gln mutation was associated with increased levels of reactive oxygen species (ROS) in spermatozoa and decreased sperm motility.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran.

    ,

    Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran. Electronic address: dor_kordi@science.usb.ac.ir.

    ,

    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: m.totonchi@royaninstitute.org.

    Source

    Gene 699: 2019 May 30 pg 16-23

    MeSH

    Amino Acid Sequence
    Asthenozoospermia
    Case-Control Studies
    Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
    Homozygote
    Humans
    Infertility, Male
    Iran
    Male
    Mutation
    Pedigree
    Reactive Oxygen Species
    Semen
    Sequence Alignment
    Sperm Motility
    Spermatozoa
    Whole Exome Sequencing

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30849544

    Citation

    Askari, Masomeh, et al. "Identification of a Homozygous GFPT2 Variant in a Family With Asthenozoospermia." Gene, vol. 699, 2019, pp. 16-23.
    Askari M, Kordi-Tamandani DM, Almadani N, et al. Identification of a homozygous GFPT2 variant in a family with asthenozoospermia. Gene. 2019;699:16-23.
    Askari, M., Kordi-Tamandani, D. M., Almadani, N., McElreavey, K., & Totonchi, M. (2019). Identification of a homozygous GFPT2 variant in a family with asthenozoospermia. Gene, 699, pp. 16-23. doi:10.1016/j.gene.2019.02.060.
    Askari M, et al. Identification of a Homozygous GFPT2 Variant in a Family With Asthenozoospermia. Gene. 2019 May 30;699:16-23. PubMed PMID: 30849544.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Identification of a homozygous GFPT2 variant in a family with asthenozoospermia. AU - Askari,Masomeh, AU - Kordi-Tamandani,Dor Mohammad, AU - Almadani,Navid, AU - McElreavey,Kenneth, AU - Totonchi,Mehdi, Y1 - 2019/03/05/ PY - 2018/07/22/received PY - 2019/02/12/revised PY - 2019/02/22/accepted PY - 2019/3/9/pubmed PY - 2019/4/16/medline PY - 2019/3/9/entrez KW - Asthenozoospermia KW - GFPT2 KW - Reactive oxygen species KW - Whole-exome sequencing SP - 16 EP - 23 JF - Gene JO - Gene VL - 699 N2 - PURPOSE: Asthenozoospermia (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. METHODS: Whole-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. RESULTS: A 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. CONCLUSION: Homozygosity of the GFPT2 p.Arg366Gln mutation was associated with increased levels of reactive oxygen species (ROS) in spermatozoa and decreased sperm motility. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/30849544/Identification_of_a_homozygous_GFPT2_variant_in_a_family_with_asthenozoospermia L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(19)30194-5 DB - PRIME DP - Unbound Medicine ER -