Solving a case of allelic dropout in the GNPTAB gene: implications in the molecular diagnosis of mucolipidosis type III alpha/beta

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Coutinho, MF (Autor) Outra; Encarnacao, M (Autor) Outra; Laranjeira, F (Autor) Outra; Lacerda, L (Autor) Outra; Prata, MJ (Autor) FCUP; Alves, S (Autor) Outra

Revista

Título: Journal of Pediatric Endocrinology and Metabolism

Vol. 29

Páginas: 1225-1228

ISSN: 0334-018X

Editora: Walter De Gruyter

Indexação

ISI Web of Knowledge - 4 Citações

Outras Informações

ID Authenticus: P-00M-4AV

DOI: 10.1515/jpem-2016-0173

Abstract (EN): While being well known that the diagnosis of many genetic disorders relies on a combination of clinical suspicion and confirmatory genetic testing, not rarely, however, genetic testing needs much perseverance and cunning strategies to identify the causative mutation(s). Here we present a case of a thorny molecular diagnosis of mucolipidosis type III alpha/beta, which is an autosomal recessive lysosomal storage disorder, caused by a defect in the GNPTAB gene that codes for the alpha/beta-subunits of the GlcNAc-1-phosphotransferase. We used both cDNA and gDNA analyses to characterize a mucolipidosis type III alpha/beta patient whose clinical diagnosis was already confirmed biochemically. In a first stage only one causal mutation was identified in heterozygosity, the already described missense mutation c.1196C>T(p.S399F), both at cDNA and gDNA levels. Only after conducting inhibition of nonsense-mediated mRNA decay (NMD) assays and after the utilization of another pair of primers the second mutation, the c.3503_3504delTC deletion, was identified. Our findings illustrate that allelic dropout due to the presence of polymorphisms and/or of mutations that trigger the NMD pathway can cause difficulties in current molecular diagnosis tests.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 4