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

Laboratoire de neurogénétique de la motricité, Neuromics Center for Excellence of Université de Montréal, CRCHUM, 1560 Sherbrooke East, Montreal, Quebec, H2L 4M1, Canada.
Neurogenetics (Impact Factor: 2.88). 10/2010; 11(4):457-64. DOI: 10.1007/s10048-010-0251-8
Source: PubMed


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.

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Available from: Geneviève Bernard, Feb 10, 2015
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    • "Hypomyelinating disorders are numerous, and the growing list of these disorders includes Pelizaeus–Merzbacher disease, Pelizaeus–Merzbacher-like disease , hypomyelination with atrophy of the basal ganglia and cerebellum, and hypomyelination with congenital cataracts. Recently, mutations of POLR3A and POLR3B, which encode the largest and second largest subunits of RNA polymerase III (Pol III), have been reported to cause allelic Pol III-related hypomyelinating disorders [2] [3] [4], including hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome ) [5], leukodystrophy with oligodontia [6], tremor-ataxia with central hypomyelination [7], and diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC) [8]. MRI in patients with clinically diagnosed 4H syndrome revealed cerebellar atrophy in addition to hypomyelination [1]. "
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