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A Point Mutation in the Coding Sequence of the β‐Hexosaminidase α Gene Results in Defective Processing of the Enzyme Protein in an Unusual GM2‐Gangliosidosis Variant
Author(s) -
Nakano Takeshi,
Muscillo Michele,
Ohno Kousaku,
Hoffman Andrew J.,
Suzuki Kunihiko
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb01836.x
Subject(s) - transversion , gangliosidosis , sandhoff disease , nucleic acid sequence , complementary dna , coding region , biochemistry , microbiology and biotechnology , point mutation , hexosaminidase , biology , peptide sequence , gene , nucleotide , enzyme , sequence analysis , amino acid , protein primary structure , mutation
cDNA clones were isolated from cultured fibro‐blasts of a patient previously reported as having GM2‐gangliosidosis due to defective processing of the precursor β‐hexosaminidase α chain. Sequence analysis of a clone containing the entire protein coding sequence showed a single nucleotide substitution, from G to A, at nucleotide residue no. 1444, which resulted in a change in amino acid residue no. 482, from the normal glutamic acid to lysine. This transversion was confirmed in two other cDNAs from the same unamplified library. The results collectively indicate that the change from the strongly negative to strongly positive charge at amino acid residue no. 482 is responsible for the defective processing of the enzyme in this patient.