Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations. Issue 5 (17th July 2019)

• Record Type: Journal Article
• Authors: Kherraf, Zine‐Eddine; Cazin, Caroline; Coutton, Charles; Amiri‐Yekta, Amir; Martinez, Guillaume; Boguenet, Magalie; Fourati Ben Mustapha, Selima; Kharouf, Mahmoud; Gourabi, Hamid; Hosseini, Seyedeh Hanieh; Daneshipour, Abbas; Touré, Aminata; Thierry‐Mieg, Nicolas; Zouari, Raoudha; Arnoult, Christophe; Ray, Pierre F.
• Is Part Of: Clinical genetics. Volume 96:Issue 5(2019)
• Page Start: 394
• Page End: 401
• Publication Date: 2019-07-17
• Subjects: flagella -- gene defects -- genetic diagnosis -- male infertility -- spermatogenesis -- whole exome sequencing; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13604
• Languages: English
• ISSNs: 0009-9163

Abstract

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. Abstract :