Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann–Pick disease

Bhavani, Gandham SriLakshmi and Girisha, KM (2016) Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann–Pick disease. American Journal of Medical Genetics Part-A, 170 (10). pp. 2719-2730.

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Acid sphingomyelinase (ASM)-deficient Niemann–Pick disease is an autosomal recessive lysosomal storage disorder caused by biallelic mutations in the SMPD1 gene. To date, around 185 mutations have been reported in patients with ASM-deficient NPD world-wide, but the mutation spectrum of this disease in India has not yet been reported. The aim of this study was to ascertain the mutation profile in Indian patients with ASM-deficien. NPD. We sequenced SMPD1 in 60 unrelated families affected with ASM-deficient NPD. A total of 45 distinct pathogenic sequence variants were found, of which 14 were known and 31 were novel. The variants included 30 missense, 4 nonsense, and 9 frameshift (7 single base deletions and 2 single base insertions) mutations, 1 indel, and 1 intronic duplication. The pathogenicity of the novel mutations was inferred with the help of the mutation prediction software MutationTaster, SIFT, Polyphen-2, PROVEAN, and HANSA. The effects of the identified sequence variants on the protein structure were studied using the structure modeled with the help of the SWISS-MODEL workspace program. The p. (Arg542) (c.1624C>T) mutation was the most commonly identified mutation, found in 22% (26 out of 120) of the alleles tested, but haplotype analysis for this mutation did not identify a founder effect for the Indian population. To the best of our knowledge, this is the largest study on mutation analysis of patients with ASM-deficient Niemann–Pick disease reported in literature and also the first study on the SMPD1 gene mutation spectrum in India.

Item Type: Article
Uncontrolled Keywords: Niemann–Pick disease; acid sphingomyelinase deficiency; SMPD1 gene mutation; India.
Subjects: Medicine > KMC Manipal > Paediatrics
Depositing User: KMC Library
Date Deposited: 26 Sep 2016 10:46
Last Modified: 26 Sep 2016 10:46
URI: http://eprints.manipal.edu/id/eprint/147020

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