Mutation analysis in patients with total sperm immotility

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

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

Revista

Título: Journal of Assisted Reproduction and Genetics

Vol. 32

Páginas: 893-902

ISSN: 1058-0468

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 33 Citações

Scopus - 35 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10