Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect.
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.
Santoro
Massimo
M
Institute of Neurology, Department of Neuroscience, Catholic University of Sacred Heart, L go A Gemelli 8, Rome, Italy.
Modoni
Anna
A
Sabatelli
Mario
M
Madia
Francesca
F
Piemonte
Fiorella
F
Tozzi
Giulia
G
Ricci
Enzo
E
Tonali
Pietro A
PA
Silvestri
Gabriella
G
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
D012333:RNA, Messenger; D054819:Hexosaminidase B; D001619:beta-N-Acetylhexosaminidases