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Journal Articles Journal of Medical Genetics Year : 2020

Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency

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Abdellah Tebani
  • Function : Author
Bénédicte Sudrié-Arnaud
  • Function : Author
Ivana Dabaj
  • Function : Author
Stéphanie Torre
  • Function : Author
Laur Domitille
  • Function : Author
Sarah Snanoudj
Benedicte Heron
  • Function : Author
Thierry Levade
  • Function : Author
Catherine Caillaud
  • Function : Author
Sabrina Vergnaud
  • Function : Author
Pascale Saugier-Veber
  • Function : Author
Sophie Coutant
  • Function : Author
Hélène Dranguet
  • Function : Author
Roseline Froissart
  • Function : Author
Majed Al Khouri
  • Function : Author
Yves Alembik
  • Function : Author
Julien Baruteau
  • Function : Author
Jean-Baptiste Arnoux
  • Function : Author
Anais Brassier
  • Function : Author
Anne-Claire Brehin
  • Function : Author
Tiffany Busa
  • Function : Author
Aline Cano
  • Function : Author
Brigitte Chabrol
  • Function : Author
Christine Coubes
  • Function : Author
Isabelle Desguerre
  • Function : Author
Martine Doco-Fenzy
  • Function : Author
Bernard Drenou
  • Function : Author
Nursel Elcioglu
  • Function : Author
Solaf Elsayed
  • Function : Author
Alain Fouilhoux
  • Function : Author
Céline Poirsier
  • Function : Author
Alice Goldenberg
  • Function : Author
Philippe Jouvencel
  • Function : Author
François Labarthe
  • Function : Author
Leila Lazaro
  • Function : Author
Samia Pichard
  • Function : Author
Serge Rivera
  • Function : Author
Sandrine Roche
  • Function : Author
Stéphanie Roggerone
  • Function : Author
Agathe Roubertie
Sabine Sigaudy
  • Function : Author
Marta Spodenkiewicz
  • Function : Author
Marine Tardieu
  • Function : Author
Catherine Vanhulle
  • Function : Author
Stéphane Marret
  • Function : Author

Abstract

Introduction This 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). Methods Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed. Results The 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. Conclusion This 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.

Dates and versions

hal-03797489 , version 1 (04-10-2022)

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Abdellah Tebani, Bénédicte Sudrié-Arnaud, Ivana Dabaj, Stéphanie Torre, Laur Domitille, et al.. Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency. Journal of Medical Genetics, 2020, 59 (4), pp.377-384. ⟨10.1136/jmedgenet-2020-107510⟩. ⟨hal-03797489⟩
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