title: Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect.
abstract: We identified a novel c.1556A>G transition in exon 12 of the HEXB gene associated with chronic Sandhoff's disease, changing a conserved aspartic acid to glycine at position 494 of the Hex beta-subunit; moreover, RT-PCR showed aberrant exon 12 skipping, causing a frame-shift and premature stop codon, consequent to the disruption of an exonic splicing enhancer motif by the mutation. These data suggest that the c.1556 A>G transition would affect both HEXB mRNA processing and biochemical properties of the beta-subunit.
authors.affiliation: Institute of Neurology, Department of Neuroscience, Catholic University of Sacred Heart, L go A Gemelli 8, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Anna
authors.initials: A
authors.lastname: Modoni
authors.forename: Mario
authors.initials: M
authors.lastname: Sabatelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Madia
authors.forename: Fiorella
authors.initials: F
authors.lastname: Piemonte
authors.forename: Giulia
authors.initials: G
authors.lastname: Tozzi
authors.forename: Enzo
authors.initials: E
authors.lastname: Ricci
authors.forename: Pietro A
authors.initials: PA
authors.lastname: Tonali
authors.forename: Gabriella
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000595:Amino Acid Sequence; D005091:Exons; D005260:Female; D054819:Hexosaminidase B; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D012333:RNA, Messenger / Q000378:metabolism; D012497:Sandhoff Disease / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D054819:Hexosaminidase B; D001619:beta-N-Acetylhexosaminidases