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01-04-2016 | Short Communication

Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia

Authors: Yi-Hong Shao, Karine Choquet, Roberta La Piana, Martine Tétreault, Marie-Josée Dicaire, Kym M. Boycott, Jacek Majewski, Bernard Brais, Care4Rare Canada Consortium

Published in: Neurogenetics | Issue 2/2016

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.

Liao P, Gelinas J, Sirrs S (2014) Phenotypic variability of Krabbe disease across the lifespan. Can J Neurol Sci 41(1):5–12CrossRefPubMed

Debs R et al (2013) Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review. J Inherit Metab Dis 36(5):859–868CrossRefPubMed

Wenger DA (1993) Krabbe disease. In: Pagon RA (ed) GeneReviews(R), Seattle

Kardas F et al (2013) A novel homozygous GALC mutation: very early onset and rapidly progressive Krabbe disease. Gene 517(1):125–127CrossRefPubMed

Graziano AC, Cardile V (2015) History, genetic, and recent advances on Krabbe disease. Gene 555(1):2–13CrossRefPubMed

Suzuki K (2003) Globoid cell leukodystrophy (Krabbe’s disease): update. J Child Neurol 18(9):595–603CrossRefPubMed

Matthes F et al (2015) Enzyme replacement therapy of a novel humanized mouse model of globoid cell leukodystrophy. Exp Neurol 271:36–45CrossRefPubMed

Farina L et al (2000) MR imaging and proton MR spectroscopy in adult Krabbe disease. AJNR Am J Neuroradiol 21(8):1478–1482PubMed

Duffner PK et al (2012) Later onset phenotypes of Krabbe disease: results of the world-wide registry. Pediatr Neurol 46(5):298–306CrossRefPubMed

10.

Li H et al (2009) The sequence alignment/Map format and SAMtools. Bioinformatics 25(16):2078–2079CrossRefPubMedPubMedCentral

11.

Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38(16), e164CrossRefPubMedPubMedCentral

12.

Tetreault M et al (2015) Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome. Hum Genet 134(9):981–991CrossRefPubMed

13.

Luzi P, Rafi MA, Wenger DA (1996) Multiple mutations in the GALC gene in a patient with adult-onset Krabbe disease. Ann Neurol 40(1):116–119CrossRefPubMed

14.

Adzhubei IA et al (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248–249CrossRefPubMedPubMedCentral

15.

Laberge AM et al (2005) Population history and its impact on medical genetics in Quebec. Clin Genet 68(4):287–301CrossRefPubMed

16.

Loes DJ, Peters C, Krivit W (1999) Globoid cell leukodystrophy: distinguishing early-onset from late-onset disease using a brain MR imaging scoring method. AJNR Am J Neuroradiol 20(2):316–323PubMed

Title: Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia
Authors: Yi-Hong Shao
Karine Choquet
Roberta La Piana
Martine Tétreault
Marie-Josée Dicaire
Kym M. Boycott
Jacek Majewski
Bernard Brais
Care4Rare Canada Consortium
Publication date: 01-04-2016
Publisher: Springer Berlin Heidelberg
Published in: Neurogenetics / Issue 2/2016
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-016-0476-2

At a glance: The STEP trials

Springer Medicine

Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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