• PMID: 31292949
• Gene Name: QRICH2
• Condition: Multiple morphological anomalies of the sperm flagella (MMAF syndrome), Male infertility
• Association: Associated
• Mutation: c.3501C>G [p.Tyr1167Ter] and c.4614C>G [p.Tyr1538Ter], c.4855+4_4855+7delAGTG, c.4119G>A p.Met1373Ile, c.3587C>T p.Pro1196Leu, c.3433G>A p.Glu1145Lys, c.3278A>G p.Glu1093Gly, c.3081A>G p.Ala1027Ala, c.290_291delTC p.Ser97TyrfsTer7, c.4618C>T p.Arg1540Tr
• Population size: 169
• Population details: 169 (2 families), 167 MMAF-affected subjects
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations

Kherraf ZE, Cazin C, Coutton C, Amiri-Yekta A, Martinez G, Boguenet M, Fourati Ben Mustapha S, Kharouf M, Gourabi H, Hosseini SH, Daneshipour A, Touré A, Thierry-Mieg N, Zouari R, Arnoult C, Ray PF.

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. CI - © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Kherraf, Zine-Eddine AU - Kherraf ZE AD - INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. AD - UM GI-DPI, CHU Grenoble Alpes, Grenoble, France. FAU - Cazin, Caroline AU - Cazin C AD - INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. AD - UM GI-DPI, CHU Grenoble Alpes, Grenoble, France. FAU - Coutton, Charles AU - Coutton C AUID- ORCID: 0000-0002-8873-8098 AD - INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. AD - UM de Génétique Chromosomique, CHU Grenoble Alpes, Grenoble, France. FAU - Amiri-Yekta, Amir AU - Amiri-Yekta A AD - INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. AD - UM GI-DPI, CHU Grenoble Alpes, Grenoble, France. AD - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. FAU - Martinez, Guillaume AU - Martinez G AD - INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. AD - UM de Génétique Chromosomique, CHU Grenoble Alpes, Grenoble, France. FAU - Boguenet, Magalie AU - Boguenet M AD - INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France. FAU - Fourati Ben Mustapha, Selima AU - Fourati Ben Mustapha S AD - Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia. FAU - Kharouf, Mahmoud AU - Kharouf M AD - Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia. FAU - Gourabi, Hamid AU - Gourabi H AD - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. FAU - Hosseini, Seyedeh Hanieh AU - Hosseini SH AD - Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. FAU - Daneshipour, Abbas AU - Daneshipour A AD - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. FAU - Touré, Aminata AU - Touré A AD - INSERM U1016, Institut Cochin, Paris, France. AD - UMR8104, Centre National de la Recherche Scientifique, Paris, France. AD - Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. FAU - Thierry-Mieg, Nicolas AU - Thierry-Mieg N AD - CNRS, TIMC-IMAG, Université Grenoble Alpes, Grenoble, France. FAU - Zouari, Raoudha AU - Zouari R AD - Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia. FAU - Arnoult, Christophe AU - Arnoult C AD - INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, Université Grenoble Alpes, Grenoble, France.