Abstract
Mutations in GALC cause Krabbe disease. This autosomal recessive leukodystrophy generally presents in early infancy as a severe disorder, but sometimes manifests as a milder adult-onset disease with spastic paraplegia as the main symptom. We recruited a family with five affected individuals presenting with adult-onset predominant cerebellar ataxia with mild spasticity. Whole exome sequencing (WES) revealed one novel and one previously reported compound heterozygous variants in GALC. Magnetic resonance imaging (MRI) confirmed the presence of typical Krabbe features. Our findings expand the phenotypic spectrum of adult-onset Krabbe disease and demonstrate the usefulness of combining WES and pattern-specific MRI for the diagnosis of neurodegenerative diseases.
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Acknowledgments
We thank the patients and their relatives who accepted to partake in this study. This work was supported by the Fondation Groupe Monaco and the Care4Rare Canada Consortium, funded in part by Genome Canada, the Canadian Institutes of Health Research (CIHR), the Ontario Genomics Institute, Ontario Research Fund, Genome Quebec, and the Children’s Hospital of Eastern Ontario Foundation. The authors wish to acknowledge the contribution of the high throughput sequencing platform of the McGill University and Génome Québec Innovation Centre, Montréal, Canada. KC and RLP received a doctoral award from the Fonds de recherche du Québec—Santé (FRQS). MT received a post-doctoral award from the Réseau de Médecine Génétique Appliquée, FRQS, and CIHR.
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The authors declare that the experiments comply with the current laws of Canada, the country in which they were performed. All participating family members signed an informed consent form approved by the institutional ethics committee of the Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), where they were initially examined.
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The authors declare that they have no conflict of interest.
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Yi-Hong Shao and Karine Choquet contributed equally to this work.
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Shao, YH., Choquet, K., La Piana, R. et al. Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia. Neurogenetics 17, 137–141 (2016). https://doi.org/10.1007/s10048-016-0476-2
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DOI: https://doi.org/10.1007/s10048-016-0476-2