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

• Type: Article in International Scientific Journal
• Date: 2016

Authors

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

Journal

Title: Journal of Pediatric Endocrinology and Metabolism

Vol. 29

Pages: 1225-1228

ISSN: 0334-018X

Publisher: Walter De Gruyter

Indexing

ISI Web of Knowledge - 4 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 4