neurogenetics

, Volume 11, Issue 4, pp 457–464

Tremor–ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3–10q23.31

  • Geneviève Bernard
  • Isabelle Thiffault
  • Martine Tetreault
  • Maria Lisa Putorti
  • Isabelle Bouchard
  • Michel Sylvain
  • Serge Melançon
  • Rachel Laframboise
  • Pierre Langevin
  • Jean-Pierre Bouchard
  • Michel Vanasse
  • Adeline Vanderver
  • Guillaume Sébire
  • Bernard Brais
ORIGINAL ARTICLE

DOI: 10.1007/s10048-010-0251-8

Cite this article as:
Bernard, G., Thiffault, I., Tetreault, M. et al. Neurogenetics (2010) 11: 457. doi:10.1007/s10048-010-0251-8

Abstract

Leukodystrophies are a heterogeneous group of disorders associated with abnormal central nervous system white matter. The clinical features invariably include upper motor neuron signs and developmental regression with or without other neurological manifestations. The objective of this study was to characterize clinically and genetically a new form of childhood-onset leukodystrophy with ataxia and tremor. We recruited seven French-Canadian cases belonging to five families affected by an unknown form of childhood-onset leukodystrophy. Genome-wide scans (GWS) were performed using the Illumina Hap310 or Hap610 Bead Chip to identify regions of shared homozygosity that were further studied for linkage with STS markers. All cases presented between the ages of 1 and 5 years with spasticity along with other upper motor neuron signs, prominent postural tremor, and cerebellar signs. Though motor regression is a constant feature, cognitive functions are relatively preserved, even late in the course of the disease. The higher frequency of founder diseases in the French-Canadian population and the segregation in pedigrees are suggestive of a recessive mode of inheritance. By homozygosity mapping, we established linkage to a 12.6-Mb SNP-haplotyped region on chromosome 10q22.3–10q23.31 (maximum LOD score: 5.47). We describe an autosomal recessive childhood-onset leukodystrophy with ataxia and tremor mapping to a 12.6 Mb interval on chromosome 10q22.3–10q23.31. Identification of the mutated gene will allow precise diagnosis and genetic counseling and shed light on how its perturbed function leads to white matter abnormalities.

Keywords

LeukodystrophyWhite matter diseaseHypomyelinationAtaxiaTremorLinkage

Supplementary material

10048_2010_251_MOESM1_ESM.doc (177 kb)
Table S1(DOC 177 kb)

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Geneviève Bernard
    • 1
  • Isabelle Thiffault
    • 1
  • Martine Tetreault
    • 1
  • Maria Lisa Putorti
    • 1
  • Isabelle Bouchard
    • 2
  • Michel Sylvain
    • 2
  • Serge Melançon
    • 3
  • Rachel Laframboise
    • 2
  • Pierre Langevin
    • 2
  • Jean-Pierre Bouchard
    • 4
  • Michel Vanasse
    • 5
  • Adeline Vanderver
    • 6
  • Guillaume Sébire
    • 7
  • Bernard Brais
    • 1
    • 8
  1. 1.Laboratoire de neurogénétique de la motricitéNeuromics Center for Excellence of Université de Montréal, CRCHUMMontrealCanada
  2. 2.CHUQ, Centre Mère-EnfantQuebecCanada
  3. 3.Montreal Children’s HospitalMcGill UniversityMontrealQuebecCanada
  4. 4.Department of Neurological SciencesCHA-Hôpital Enfant-JésusQuebecCanada
  5. 5.Neurology DepartmentCHU-Hôpital Ste-JustineMontrealCanada
  6. 6.Children’s National Medical Center, Children’s Research InstituteCenter for Genetic Medicine ResearchWashington DCUSA
  7. 7.CHUS, Sherbrooke UniversitySherbrookeCanada
  8. 8.Laboratoire de neurogénétique de la motricité, M4211-L3Hôpital Notre-Dame-CHUM, CRCHUMMontrealCanada