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Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations.
Clin Genet. 2019 11; 96(5):394-401.CG

Abstract

Multiple morphological anomalies of the sperm flagella (MMAF syndrome) is a severe male infertility phenotype which has so far been formally linked to the presence of biallelic mutations in nine genes mainly coding for axonemal proteins overexpressed in the sperm flagellum. Homozygous mutations in QRICH2, a gene coding for a protein known to be required for stabilizing proteins involved in sperm flagellum biogenesis, have recently been identified in MMAF patients from two Chinese consanguineous families. Here, in order to better assess the contribution of QRICH2 in the etiology of the MMAF phenotype, we analyzed all QRICH2 variants from whole exome sequencing data of a cohort of 167 MMAF-affected subjects originating from North Africa, Iran, and Europe. We identified a total of 14 potentially deleterious variants in 18 unrelated individuals. Two unrelated subjects, representing 1% of the cohort, carried a homozygous loss-of-function variant: c.3501C>G [p.Tyr1167Ter] and c.4614C>G [p.Tyr1538Ter], thus confirming the implication of QRICH2 in the MMAF phenotype and human male infertility. Sixteen MMAF patients (9.6%) carried a heterozygous QRICH2 potentially deleterious variant. This rate was comparable to what was observed in a control group (15.5%) suggesting that the presence of QRICH2 heterozygous variants is not associated with MMAF syndrome.

Authors+Show Affiliations

INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. UM GI-DPI, CHU Grenoble Alpes, Grenoble, France.INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. UM GI-DPI, CHU Grenoble Alpes, Grenoble, France.INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. UM de Génétique Chromosomique, CHU Grenoble Alpes, Grenoble, France.INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. UM GI-DPI, CHU Grenoble Alpes, Grenoble, France. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. UM de Génétique Chromosomique, CHU Grenoble Alpes, Grenoble, France.INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France.Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia.Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia.Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.INSERM U1016, Institut Cochin, Paris, France. UMR8104, Centre National de la Recherche Scientifique, Paris, France. Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.CNRS, TIMC-IMAG, Université Grenoble Alpes, Grenoble, France.Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia.INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France.INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. UM GI-DPI, CHU Grenoble Alpes, Grenoble, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31292949

Citation

Kherraf, Zine-Eddine, et al. "Whole Exome Sequencing of Men With Multiple Morphological Abnormalities of the Sperm Flagella Reveals Novel Homozygous QRICH2 Mutations." Clinical Genetics, vol. 96, no. 5, 2019, pp. 394-401.
Kherraf ZE, Cazin C, Coutton C, et al. Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations. Clin Genet. 2019;96(5):394-401.
Kherraf, Z. E., Cazin, C., Coutton, C., Amiri-Yekta, A., Martinez, G., Boguenet, M., Fourati Ben Mustapha, S., Kharouf, M., Gourabi, H., Hosseini, S. H., Daneshipour, A., Touré, A., Thierry-Mieg, N., Zouari, R., Arnoult, C., & Ray, P. F. (2019). Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations. Clinical Genetics, 96(5), 394-401. https://doi.org/10.1111/cge.13604
Kherraf ZE, et al. Whole Exome Sequencing of Men With Multiple Morphological Abnormalities of the Sperm Flagella Reveals Novel Homozygous QRICH2 Mutations. Clin Genet. 2019;96(5):394-401. PubMed PMID: 31292949.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations. AU - Kherraf,Zine-Eddine, AU - Cazin,Caroline, AU - Coutton,Charles, AU - Amiri-Yekta,Amir, AU - Martinez,Guillaume, AU - Boguenet,Magalie, AU - Fourati Ben Mustapha,Selima, AU - Kharouf,Mahmoud, AU - Gourabi,Hamid, AU - Hosseini,Seyedeh Hanieh, AU - Daneshipour,Abbas, AU - Touré,Aminata, AU - Thierry-Mieg,Nicolas, AU - Zouari,Raoudha, AU - Arnoult,Christophe, AU - Ray,Pierre F, Y1 - 2019/07/17/ PY - 2019/05/10/received PY - 2019/06/28/revised PY - 2019/07/08/accepted PY - 2019/7/12/pubmed PY - 2020/9/1/medline PY - 2019/7/12/entrez KW - flagella KW - gene defects KW - genetic diagnosis KW - male infertility KW - spermatogenesis KW - whole exome sequencing SP - 394 EP - 401 JF - Clinical genetics JO - Clin. Genet. VL - 96 IS - 5 N2 - Multiple morphological anomalies of the sperm flagella (MMAF syndrome) is a severe male infertility phenotype which has so far been formally linked to the presence of biallelic mutations in nine genes mainly coding for axonemal proteins overexpressed in the sperm flagellum. Homozygous mutations in QRICH2, a gene coding for a protein known to be required for stabilizing proteins involved in sperm flagellum biogenesis, have recently been identified in MMAF patients from two Chinese consanguineous families. Here, in order to better assess the contribution of QRICH2 in the etiology of the MMAF phenotype, we analyzed all QRICH2 variants from whole exome sequencing data of a cohort of 167 MMAF-affected subjects originating from North Africa, Iran, and Europe. We identified a total of 14 potentially deleterious variants in 18 unrelated individuals. Two unrelated subjects, representing 1% of the cohort, carried a homozygous loss-of-function variant: c.3501C>G [p.Tyr1167Ter] and c.4614C>G [p.Tyr1538Ter], thus confirming the implication of QRICH2 in the MMAF phenotype and human male infertility. Sixteen MMAF patients (9.6%) carried a heterozygous QRICH2 potentially deleterious variant. This rate was comparable to what was observed in a control group (15.5%) suggesting that the presence of QRICH2 heterozygous variants is not associated with MMAF syndrome. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/31292949/Whole_exome_sequencing_of_men_with_multiple_morphological_abnormalities_of_the_sperm_flagella_reveals_novel_homozygous_QRICH2_mutations_ L2 - https://doi.org/10.1111/cge.13604 DB - PRIME DP - Unbound Medicine ER -