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Genetic cause of a juvenile form of tay‐sachs disease in a lebanese child
Author(s) -
Boustany RoseMary N.,
Tanaka Akemi,
Nishimoto Junji,
Suzuki Kunihiko
Publication year - 1991
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410290120
Subject(s) - tay sachs disease , exon , hexosaminidase , compound heterozygosity , cousin , genetics , mutation , biology , polymerase chain reaction , allele , point mutation , ataxia , microbiology and biotechnology , gene , disease , medicine , biochemistry , enzyme , history , archaeology , neuroscience
Abnormality in the β‐hexosaminidase α gene underlying the clinical phenotype of a Lebanese patient with a juvenile form of Tay‐Sachs disease has been studied. Clinical features were progressive spasticity, ataxia, and cognitive decline. The protein coding sequence of several β‐hexosaminidase α‐chain complementary DNAs isolated by polymerase chain reaction was completely normal except for a G‐to‐A transition at nucleotide position 1511 within exon 13, which resulted in substitution of the normal arginine 504 (CGC) with histidine (CAC). Although the patient was from a first‐cousin marriage, she was heterozygous for this mutation. The abnormality in the other allele, which is carried by the father, was not identified, except that it is neither of the two mutations responsible for the infantile Jewish Tay‐Sachs disease. Biosynthetic and immunoprecipitation studies in cultured fibroblasts showed synthesis of the α‐chain precursor, but the mature form of the α‐subunit was not detected.