Journal Article

A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome

Andrea Balreira, Paulo Gaspar, Daniel Caiola, João Chaves, Idalina Beirão, José Lopes Lima, Jorge Eduardo Azevedo and Maria Clara Sá Miranda

in Human Molecular Genetics

Volume 17, issue 14, pages 2238-2243
Published in print July 2008 | ISSN: 0964-6906
Published online April 2008 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddn124
A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome

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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 β-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 β-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 β-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.

Journal Article.  3660 words.  Illustrated.

Subjects: Genetics and Genomics

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