Development of a multiplex ligation-dependent probe amplification assay for diagnosis and estimation of the frequency of spinocerebellar ataxia type 15

Abstract

BACKGROUND: Spinocerebellar ataxia type 15 (SCA15) is a slowly progressive neurodegenerative disorder characterized by cerebellar ataxia. Mutation of the ITPR1 gene (inositol 1,4,5-triphosphate receptor, type 1) has been identified recently as the underlying cause, and in most cases the molecular defect is a multiexon deletion. To date, 5 different SCA15 families have been identified with ITPR1 gene deletion. METHODS: We have designed a synthetic, dual-color multiplex ligation-dependent probe amplification (MLPA) assay that measures copy number with high precision in selected exons across the entire length of ITPR1 and the proximal region of the neighboring gene, SUMF1 (sulfatase modifying f..