title: Two mutated HEXA alleles in a Druze patient with late-infantile Tay-Sachs disease.
abstract: Two affected HEXA alleles were found in an Israeli Druze Tay-Sachs child born to first-cousin parents. His paternal allele contained two adjacent changes in exon 5: delta496C, which resulted in a frameshift and premature termination codon 96 nucleotides downstream, and 498C-->G, a silent mutation. The maternal allele had a 835T-->C transition in exon 8 (S279P). Phosphoimaging quantitation of the parents' RNAs showed that the steady-state levels of mRNAs of the mutant exons 5 and 8 were 5% and 50%, respectively, of normal levels. The exon 5 mutated allele with the premature translation termination resulted in severe deficiency of Hex A. Transient expression of the exon 8 mutated alpha-chain cDNA in COS-1 cells resulted in deficiency of enzymatic activity. The child exhibited a late-infantile-type disease.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Drucker
authors.forename: J A
authors.initials: JA
authors.lastname: Hemli
authors.forename: R
authors.initials: R
authors.lastname: Navon
mesh_terms: D000483:Alleles; D000818:Animals; D019556:COS Cells; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005796:Genes / Q000235:genetics; D054818:Hexosaminidase A; D006801:Humans; D007557:Israel; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics*; D014162:Transfection; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases