title: Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia.
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.
authors.affiliation: Neurogenetics of Motion Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada.
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Shao
authors.affiliation: Neurogenetics of Motion Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada.|Department of Human Genetics, McGill University, Montreal, QC, H3A 1B1, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Choquet
authors.affiliation: Neurogenetics of Motion Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada.
authors.forename: Roberta
authors.initials: R
authors.lastname: La Piana
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC, H3A 1B1, Canada.|McGill University and Genome Quebec Innovation Center, Montreal, QC, Canada.
authors.forename: Martine
authors.initials: M
authors.lastname: Tétreault
authors.affiliation: Neurogenetics of Motion Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Dicaire
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC, H3A 1B1, Canada.|McGill University and Genome Quebec Innovation Center, Montreal, QC, Canada.
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.affiliation: Neurogenetics of Motion Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada. bernard.brais@mcgill.ca.|Department of Human Genetics, McGill University, Montreal, QC, H3A 1B1, Canada. bernard.brais@mcgill.ca.
authors.forename: Bernard
authors.initials: B
authors.lastname: Brais
mesh_terms: D000293:Adolescent; D000328:Adult; D002524:Cerebellar Ataxia / Q000235:genetics*; D002648:Child; D005260:Female; D005698:Galactosylceramidase / Q000235:genetics*; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D055815:Young Adult
chemical_list: D005698:Galactosylceramidase
keywords: Cerebellar ataxia; Exome sequencing; GALC; Krabbe leukodystrophy