Identification of novel mutations in HEXA gene in children affected with Tay-Sachs disease from India

Mehul Mistri,Jayesh Sheth,Sarita Gupta,Chaitanya Datar,Frenny Sheth

doi:10.1186/1755-8166-7-s1-p53

Mehul Mistri, Jayesh Sheth + Show 3 more

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https://doi.org/10.1186/1755-8166-7-s1-p53

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Abstract

Background Tay-Sachs disease (TSD) is an autosomal recessive storage disorder due to impaired activity of the lysosomal enzyme b-Hexosaminidase-A (EC 3.2.1.52) due to the mutation in HEXA gene. As per HGMD database, 134 mutations have been reported from different ethnic groups, while in India only few mutations have been reported till date. Here we reported three new novel mutations in HEXA gene causing TSD in children from Maharashtra. The objective of the investigation was to determine the disease causing mutations in HEXA gene in children affected with Tay-Sachs disease confirmed by deficient enzyme activity of b-Hexosaminidase-A.

Highlights

Tay-Sachs disease (TSD) is an autosomal recessive storage disorder due to impaired activity of the lysosomal enzyme b-Hexosaminidase-A (EC 3.2.1.52) due to the mutation in HEXA gene
In silico analysis further confirmed the pathogenic effect of the novel mutations occurred at highly evolutionarily conserved and functionally active domain residues in the protein leading to conformational changes or mRNA producing truncated protein resulting in the diminish or absent activity of the protein
We have found 3/8 (37.5%) novel mutations [D175A, G269R and R510X] in present study along with 5/8 (62.5 %) previously reported mutations [E462V, D322Y, R178C, c.1277_1278insTATC (p.Y427IfsX5) and c.459+5 G>A]

Summary

Introduction

Tay-Sachs disease (TSD) is an autosomal recessive storage disorder due to impaired activity of the lysosomal enzyme b-Hexosaminidase-A (EC 3.2.1.52) due to the mutation in HEXA gene. As per HGMD database, 134 mutations have been reported from different ethnic groups, while in India only few mutations have been reported till date. We reported three new novel mutations in HEXA gene causing TSD in children from Maharashtra. The objective of the investigation was to determine the disease causing mutations in HEXA gene in children affected with Tay-Sachs disease confirmed by deficient enzyme activity of b-Hexosaminidase-A

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