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β‐galactosidase gene mutations affecting the lysosomal enzyme and the elastin‐binding protein in GM1‐gangliosidosis patients with cardiac involvement
Author(s) -
Morrone A.,
Bardelli T.,
Donati M.A.,
Giorgi M.,
Di Rocco M.,
Gatti R.,
Parini R.,
Ricci R.,
Taddeucci G.,
D'Azzo A.,
Zammarchi E.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(200004)15:4<354::aid-humu8>3.0.co;2-l
Subject(s) - biology , gangliosidosis , mutation , exon , compound heterozygosity , gene , elastin , lysosomal storage disease , rna splicing , microbiology and biotechnology , rna , genetics , enzyme , biochemistry
GM1‐gangliosidosis is a lysosomal storage disorder caused by deficiency of acid β‐galactosidase (GLB1). We report five new β‐galactosidase gene mutations in nine Italian patients and one fetus, segregating in seven unrelated families. Six of the eight patients with the infantile, severe form of the disease presented cardiac involvement, a feature rarely associated with GM1‐gangliosidosis. Molecular analysis of the patients' RNA and DNA identified two new RNA splicing defects, three new and three previously described amino acid substitutions. Interestingly, all patients with cardiac involvement were homozygous for one of these mutations: R59H, Y591C, Y591N, or IVS14‐2A>G. In contrast, all other patients were compound heterozygous for one of the following mutations: R201H, R482H, G579D, IVS8+2T>C. Although we could not directly correlate the presence of cardiac abnormalities with specific genetic lesions, the mutations identified in patients with cardiomyopathy fell in the GLB1 cDNA region common to the lysosomal enzyme and the Hβ‐Gal‐related protein, also known as the elastin binding protein (EBP). Consequently, both molecules are affected by the mutations, and they may contribute differently to the occurrence of specific clinical manifestations. Hum Mutat 15:354–366, 2000. © 2000 Wiley‐Liss, Inc.