title: Mutation analysis of a Sandhoff disease patient in the Maronite community in Cyprus.
abstract: Sandhoff disease occurs in the Christian Maronite community in Cyprus, a community that established over a thousand years ago. Nowadays, this community comprises less than 1% of the whole population, and has been culturally and socially isolated. Cultured fibroblasts from a patient from this inbred group showed a beta-hexosaminidase beta subunit mRNA of apparently the normal size but of reduced quantity. A mutational analysis of cDNA obtained by polymerase chain reaction amplification of mRNA showed a deletion of A at nt 76 (counted from A of the initiation codon, ATG). The deletion results in a frame shift and a premature termination within 20 amino acids from the N-terminus of the normal mature enzyme protein. The patient was homozygous for the deletion. The 5'-end of the gene showed many discrepancies from the previously published sequence. We consider that these differences are probably polymorphisms of little functional significance, because the patient's fibroblasts generate decreased but stable mRNA and because some of these base changes were also found in the genes from control fibroblasts. An extensive evaluation of the prevalence of this mutant allele in this community is being initiated.
authors.affiliation: Department of Neurology, University of North Carolina School of Medicine, Chapel Hill 27599.
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: P
authors.initials: P
authors.lastname: Ioannou
authors.forename: A
authors.initials: A
authors.lastname: Drousiotou
authors.forename: G
authors.initials: G
authors.lastname: Stylianidou
authors.forename: V
authors.initials: V
authors.lastname: Anastasiadou
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D001483:Base Sequence; D003535:Cyprus; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012497:Sandhoff Disease / Q000208:ethnology / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics
chemical_list: D001619:beta-N-Acetylhexosaminidases