β-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement
A. Morrone
Department of Paediatrics, University of Florence, Florence, Italy
A. Morrone and T. Bardelli contributed equally to this work.
Search for more papers by this authorT. Bardelli
Department of Paediatrics, University of Florence, Florence, Italy
A. Morrone and T. Bardelli contributed equally to this work.
Search for more papers by this authorM.A. Donati
Department of Paediatrics, University of Florence, Florence, Italy
Search for more papers by this authorM. Giorgi
Department of Paediatrics, University of Florence, Florence, Italy
Search for more papers by this authorG. Taddeucci
Department of Paediatrics, University of Pisa, Pisa, Italy
Search for more papers by this authorA. D'Azzo
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
Search for more papers by this authorCorresponding Author
E. Zammarchi
Department of Paediatrics, University of Florence, Florence, Italy
Dipartimento di Pediatria, Università di Firenze, Azienda Ospedaliera “A. Meyer”, Via Luca Giordano 13, 50132 Firenze, ItalySearch for more papers by this authorA. Morrone
Department of Paediatrics, University of Florence, Florence, Italy
A. Morrone and T. Bardelli contributed equally to this work.
Search for more papers by this authorT. Bardelli
Department of Paediatrics, University of Florence, Florence, Italy
A. Morrone and T. Bardelli contributed equally to this work.
Search for more papers by this authorM.A. Donati
Department of Paediatrics, University of Florence, Florence, Italy
Search for more papers by this authorM. Giorgi
Department of Paediatrics, University of Florence, Florence, Italy
Search for more papers by this authorG. Taddeucci
Department of Paediatrics, University of Pisa, Pisa, Italy
Search for more papers by this authorA. D'Azzo
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
Search for more papers by this authorCorresponding Author
E. Zammarchi
Department of Paediatrics, University of Florence, Florence, Italy
Dipartimento di Pediatria, Università di Firenze, Azienda Ospedaliera “A. Meyer”, Via Luca Giordano 13, 50132 Firenze, ItalySearch for more papers by this authorAbstract
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.
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