Mutation in GM2‐Gangliosidosis B1 Variant

Abstract

Fibroblasts from a patient with GM2-gangliosidosis B1 variant contained mRNA of normal size but in reduced quantity for the β-hexosaminidase α subunit. The nucleotide sequence of a cDNA clone that included the entire protein coding sequence was completely normal except for a sinde base substitution from G to A at no. 533, resulting in a change from arginine to histidine at amino acid no. 178. The same mutation was found in two other cDNA clones. The position of the mutation is ∼90 amino acids from the N-terminus of the mature, processed enzyme. Computer analysis predicated substantial alterations in the secondary structure of the enzyme protein. These results provide new insight into functional domains of this enzyme.