Mutation analysis in patients with total sperm immotility |
| |
Authors: | Rute Pereira Jorge Oliveira Luis Ferraz Alberto Barros Rosário Santos Mário Sousa |
| |
Institution: | 1. Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (UP), Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal 2. Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre 1021/1055, 4169-007, Porto, Portugal 3. Multidisciplinary Unit for Biomedical Research-UMIB, ICBAS-UP, Porto, Portugal 4. Molecular Genetics Unit, Centre of Medical Genetics Dr. Jacinto Magalh?es (CGMJM), Hospital Centre of Porto (CHP), Pra?a Pedro Nunes, 88, 4099-028, Porto, Portugal 5. Department of Urology, Hospital Eduardo Santos Silva, Hospital Centre of Vila Nova de Gaia (CHVNG), Espinho, E.P.E., Rua Concei??o Fernandes, 4434-502, Vila Nova de Gaia, Portugal 6. Centre of Reproductive Genetics Alberto Barros (CGR), Av. do Bessa, 240, 1o Dto. Frente, 4100-012, Porto, Portugal 7. Department of Genetics, Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319, Porto, Portugal
|
| |
Abstract: | PurposePerform the genetic characterization of five patients with total sperm immotility using Sanger sequencing and Whole Exome Sequencing (WES), in order to increase the knowledge on the genetics of sperm immotility and, ultimately, allow the identification of potential genetic markers for infertility.MethodsProspective study at a University Medical school. We analysed five men with total sperm immotility, four with dysplasia of the fibrous sheath (DFS), associated with disruption of several axonemal structures, and one patient with situs inversus totalis, which showed absence of dynein arms (DA) and nexin bridges. We screened 7 genes by Sanger sequencing, involved in sperm motility and associated to ultrastructural defects found in these patients (CCDC39, CCDC40, DNAH5, DNAI1, RSPH1, AKAP3 and AKAP4). Additionally, we performed WES analysis in the patient with situs inversus.ResultsWe identified nine new DNA sequence variants by WES. Two of these variants were considered particularly relevant: a homozygous missense change in CCDC103 gene (c.104G > C, p.R35P) probably related with absence of dynein arms; the other in the INSL6 gene (c.262_263delCC) is thought to be also involved in sperm immotility.ConclusionsOur work suggests that WES is an effective strategy, especially as compared with conventional sequencing, to study highly heterogenic genetic diseases, such as sperm immotility. For future work we expect to expand the analysis of WES to the other four patients and complement findings with expression analysis or functional studies to determine the impact of the novel variants.Electronic supplementary materialThe online version of this article (doi:10.1007/s10815-015-0474-6) contains supplementary material, which is available to authorized users. |
| |
Keywords: | Dysplasia of the fibrous sheath (DFS) Genetic diagnosis situs inversus totalis Sperm immotility Whole Exome Sequencing (WES) |
本文献已被 SpringerLink 等数据库收录! |
|