Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder 
due to mutations in the HEXA gene resulting in a beta-hexosaminidase A (Hex A) 
deficiency. The purpose of this study was to characterize the molecular 
abnormalities in patients with infantile or later-onset forms of the disease. 
The complete sequencing of the 14 exons and flanking regions of the HEXA gene 
was performed with a unique technical condition in 10 unrelated TSD patients. 
Eleven mutations were identified, including five splice mutations, one 
insertion, two deletions and three single-base substitutions. Four mutations 
were novel: two splice mutations (IVS8+5G>A, IVS2+4delAGTA), one missense 
mutation in exon 6 (c.621T>G (p.D207E)) and one small deletion 
(c.1211-1212delTG) in exon 11 resulting in a premature stop codon at residue 
429. The c.621T>G missense mutation was found in a patient presenting an 
infantile form. Its putative role in the pathogenesis of TSD is suspected as 
residue 207 is highly conserved in human, mouse and rat. Moreover, structural 
modelling predicted changes likely to affect substrate binding and catalytic 
activity of the enzyme. The time-saving procedure reported here could be useful 
for the characterization of Tay-Sachs-causing mutations, in particular in 
non-Ashkenazi patients mainly exhibiting rare mutations.