A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic ep...

• Autor(es): Balreira, A. ; Gaspar, P. ; Caiola, D. ; Chaves, J. ; Beirão, I. ; Lima, J. ; Azevedo, J. ; Miranda, M.
• Data: 2008
• Identificador Persistente: http://hdl.handle.net/10400.16/885
• Origem: Repositório Científico do Centro Hospitalar do Porto
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

Abstract The main clinical features of two siblings from a consanguineous marriage were progressive myoclonic epilepsy without intellectual impairment and a nephrotic syndrome with a strong accumulation of C1q in capillary loops and mesangium of kidney. The biochemical analysis of one of the patients revealed a normal beta-glucocerebrosidase activity in leukocytes, but a severe enzymatic deficiency in cultured skin fibroblasts. This deficiency suggested a defect in the intracellular sorting pathway of this enzyme. The sequence analysis of the gene encoding LIMP-2 (SCARB2), the sorting receptor for beta-glucocerebrosidase, confirmed this hypothesis. A homozygous nonsense mutation in codon 178 of SCARB2 was found in the patient, whereas her healthy parents were heterozygous for the mutation. Besides lacking immunodetectable LIMP-2, patient fibroblasts also had decreased amounts of beta-glucocerebrosidase, which was mainly located in the endoplasmic reticulum, as assessed by its sensitivity to Endo H. This is the first report of a mutation in the SCARB2 gene associated with a human disease, which, contrary to earlier proposals, shares no features with Charcot-Marie-Tooth disease both at the clinical and neurophysiological levels.