Mutation analysis in patients with total sperm immotility

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Rute Pereira (Author) FCUP; Jorge Oliveira (Author) Other; Luis Ferraz (Author) Other; Alberto Barros (Author) Other; Rosario Santos (Author) Other; Mario Sousa (Author) Other

Journal

Title: Journal of Assisted Reproduction and Genetics

Vol. 32

Pages: 893-902

ISSN: 1058-0468

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 33 Citations

Scopus - 35 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-00G-3HC

DOI: 10.1007/s10815-015-0474-6

Abstract (EN): Perform 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. Prospective 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. We 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. Our 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10