1. Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency
- Author
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Tiffany Busa, Anaïs Brassier, Agathe Roubertie, Bénédicte Héron, M. Tardieu, Stéphane Marret, Roseline Froissart, Martine Doco-Fenzy, Céline Poirsier, Stéphanie Torre, Serge Rivera, Ivana Dabaj, Sabrina Vergnaud, Julien Baruteau, Marta Spodenkiewicz, Jean-Baptiste Arnoux, Bénédicte Sudrié-Arnaud, Brigitte Chabrol, Abdellah Tebani, Solaf M. Elsayed, Catherine Vanhulle, Sarah Snanoudj, Anne-Claire Brehin, Pascale Saugier-Veber, Aline Cano, Hélène Dranguet, Thierry Levade, Alice Goldenberg, Samia Pichard, Alice Kuster, Catherine Caillaud, Majed Al Khouri, Yves Alembik, Stéphanie Roggerone, Isabelle Desguerre, Nursel Elcioglu, François Labarthe, Sophie Coutant, Philippe Jouvencel, Bernard Drenou, Sandrine Roche, Laur Domitille, Alain Fouilhoux, Sabine Sigaudy, Christine Coubes, Soumeya Bekri, Leila Lazaro, Tebani, Abdellah, Sudrie-Arnaud, Benedicte, Dabaj, Ivana, Torre, Stephanie, Domitille, Laur, Snanoudj, Sarah, Heron, Benedicte, Levade, Thierry, Caillaud, Catherine, Vergnaud, Sabrina, Saugier-Veber, Pascale, Coutant, Sophie, Dranguet, Helene, Froissart, Roseline, Al Khouri, Majed, Alembik, Yves, Baruteau, Julien, Arnoux, Jean-Baptiste, Brassier, Anais, Brehin, Anne-Claire, Busa, Tiffany, Cano, Aline, Chabrol, Brigitte, Coubes, Christine, Desguerre, Isabelle, Doco-Fenzy, Martine, Drenou, Bernard, Elcioglu, Nursel H., Elsayed, Solaf, Fouilhoux, Alain, Poirsier, Celine, Goldenberg, Alice, Jouvencel, Philippe, Kuster, Alice, Labarthe, Francois, Lazaro, Leila, Pichard, Samia, Rivera, Serge, Roche, Sandrine, Roggerone, Stephanie, Roubertie, Agathe, Sigaudy, Sabine, Spodenkiewicz, Marta, Tardieu, Marine, Vanhulle, Catherine, Marret, Stephane, and Bekri, Soumeya
- Subjects
EXPRESSION ,0301 basic medicine ,Proband ,FIBROBLASTS ,brain diseases ,ELASTIN-BINDING PROTEIN ,GM1 GANGLIOSIDOSIS ,Mucopolysaccharidosis ,Genomics ,G(M1) Ganglioside ,Bioinformatics ,03 medical and health sciences ,Exon ,0302 clinical medicine ,metabolic ,Pregnancy ,Hydrops fetalis ,genomics ,Genetics ,medicine ,Humans ,Gene ,Genetics (clinical) ,Gangliosidosis, GM1 ,business.industry ,Mucopolysaccharidosis IV ,brain damage ,ADULTS ,GM1-GANGLIOSIDOSIS ,beta-Galactosidase ,medicine.disease ,Phenotype ,POLYMORPHISM ,chronic ,MORQUIO B DISEASE ,030104 developmental biology ,IMPAIRED ELASTOGENESIS ,GLB1 ,Mutation ,central nervous system diseases ,Female ,business ,GENE-MUTATIONS ,030217 neurology & neurosurgery - Abstract
IntroductionThis study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB).MethodsClinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed.ResultsThe clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group.ConclusionThis study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management.
- Published
- 2021
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