Can whole-exome sequencing (WES) of patients with multiple morphological abnormalities of the sperm flagella (MMAF) identify causal mutations in new genes or mutations in the previously identified dynein axonemal heavy chain 1 (DNAH1) gene?WES for six families with men affected by MMAF syndrome allowed the identification of DNAH1 mutations in four affected men distributed in two out of the six families but no new candidate genes were identified.Mutations in DNAH1, an axonemal inner dynein arm heavy chain gene, have been shown to be responsible for male infertility due to a characteristic form of asthenozoospermia called MMAF, defined by the presence in the ejaculate of spermatozoa with a mosaic of flagellar abnormalities including absent, coiled, bent, angulated, irregular and short flagella.This was a retrospective genetics study of patients presenting a MMAF phenotype. Patients were recruited in Iran and Italy between 2008 and 2015.WES was performed for a total of 10 subjects. All identified variants were confirmed by Sanger sequencing. Two additional affected family members were analyzed by direct Sanger sequencing. To establish the prevalence of the DNAH1 mutation identified in an Iranian family, we carried out targeted sequencing on 38 additional MMAF patients of the same geographical origin. RT-PCR and immunochemistry were performed on sperm samples to assess the effect of the identified mutation on RNA and protein.WES in six families identified a causal mutations in two families. Two additional affected family members were confirmed to hold the same homozygous mutation as their sibling. In total, DNAH1 mutations were identified in 5 out of 12 analyzed subjects (41.7
作者：Amir, Amiri-Yekta；Charles, Coutton；Zine-Eddine, Kherraf；Thomas, Karaouzène；Pauline, Le Tanno；Mohammad Hossein, Sanati；Marjan, Sabbaghian；Navid, Almadani；Mohammad Ali, Sadighi Gilani；Seyedeh Hanieh, Hosseini；Salahadin, Bahrami；Abbas, Daneshipour；Maurizio, Bini；Christophe, Arnoult；Roberto, Colombo；Hamid, Gourabi；Pierre F, Ray
来源：Human reproduction (Oxford, England) 2016 年 31卷 12期
