Tay Sachs disease (TSD) is a neurodegenerative disorder due to β-hexosaminidase 
A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay 
Sachs disease in India are yet unknown. We aimed to determine mutations leading 
to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion 
criteria included neuroregression, seizures, exaggerated startle reflex, 
macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging 
criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the 
brain. Biochemical criteria included deficiency of hexosaminidase A (less than 
2% of total hexosaminidase activity for infantile patients). Total leukocyte 
hexosaminidase activity was assayed by 
4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A 
activity was assayed by heat inactivation method and 
4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. The exons 
and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using 
an automated sequencer. Mutations were confirmed in parents and looked up in 
public databases. In silico analysis for mutations was carried out using SIFT, 
Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen 
families were included in the study. We identified six novel missense mutations, 
c.340 G>A (p.E114K), c.964 G>A (p.D322N), c.964 G>T (p.D322Y), c.1178C>G 
(p.R393P) and c.1385A>T (p.E462V), c.1432 G>A (p.G478R) and two previously 
reported mutations. c.1277_1278insTATC and c.508C>T (p.R170W). The mutation 
p.E462V was found in six unrelated families from Gujarat indicating a founder 
effect. A previously known splice site mutation c.805+1 G>C and another intronic 
mutation c.672+30 T>G of unknown significance were also identified. Mutations 
could not be identified in one family. We conclude that TSD patients from 
Gujarat should be screened for the common mutation p.E462V.