Abstract
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, Y59 IN, or IVS142A>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.
| Original language | English |
|---|---|
| Pages (from-to) | 354-366 |
| Number of pages | 13 |
| Journal | Human Mutation |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2000 |
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Keywords
- β-galactosidase
- Cardiomyopathy
- EBP
- Elastin binding protein
- GLB1
- GM1-gangliosidosis
- Lysosomal storage disorder
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
β-Galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement. / 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.
In: Human Mutation, Vol. 15, No. 4, 2000, p. 354-366.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - β-Galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement
AU - Morrone, A.
AU - Bardelli, T.
AU - Donati, M. A.
AU - Giorgi, M.
AU - Di Rocco, M.
AU - Gatti, R.
AU - Parini, R.
AU - Ricci, R.
AU - Taddeucci, G.
AU - D'Azzo, A.
AU - Zammarchi, E.
PY - 2000
Y1 - 2000
N2 - 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, Y59 IN, or IVS142A>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.
AB - 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, Y59 IN, or IVS142A>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.
KW - β-galactosidase
KW - Cardiomyopathy
KW - EBP
KW - Elastin binding protein
KW - GLB1
KW - GM1-gangliosidosis
KW - Lysosomal storage disorder
UR - http://www.scopus.com/inward/record.url?scp=0034035151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034035151&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1098-1004(200004)15:4<354::AID-HUMU8>3.0.CO;2-L
DO - 10.1002/(SICI)1098-1004(200004)15:4<354::AID-HUMU8>3.0.CO;2-L
M3 - Article
C2 - 10737981
AN - SCOPUS:0034035151
VL - 15
SP - 354
EP - 366
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 4
ER -