Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect

Massimo Santoro; Anna Modoni; Mario Sabatelli; Francesca Madia; Fiorella Piemonte; Giulia Tozzi; Enzo Ricci; Pietro A Tonali; Gabriella Silvestri

doi:10.1016/j.ymgme.2006.12.004

Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect

Mol Genet Metab. 2007 May;91(1):111-4. doi: 10.1016/j.ymgme.2006.12.004. Epub 2007 Jan 23.

Authors

Massimo Santoro¹, Anna Modoni, Mario Sabatelli, Francesca Madia, Fiorella Piemonte, Giulia Tozzi, Enzo Ricci, Pietro A Tonali, Gabriella Silvestri

Affiliation

¹ Institute of Neurology, Department of Neuroscience, Catholic University of Sacred Heart, L go A Gemelli 8, Rome, Italy.

PMID: 17251047
DOI: 10.1016/j.ymgme.2006.12.004

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.

MeSH terms

Amino Acid Sequence
Exons
Female
Hexosaminidase B
Humans
Male
Molecular Sequence Data
Mutation, Missense*
Pedigree
RNA, Messenger / metabolism
Sandhoff Disease / enzymology*
Sandhoff Disease / genetics*
Sandhoff Disease / metabolism
beta-N-Acetylhexosaminidases / genetics*
beta-N-Acetylhexosaminidases / metabolism

Substances

RNA, Messenger
Hexosaminidase B
beta-N-Acetylhexosaminidases

Associated data

OMIM/268800
RefSeq/NM_000521