Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p.

Giovanni Stevanin, Naima Bouslam, Stéphane Thobois, Hamid Azzedine, Lucas Ravaux, Anne Boland, Martin Schalling, Emmanuel Broussolle, Alexandra Dürr, Alexis Brice
Ann Neurol.. 2003-12-30; 55(1): 97-104
DOI: 10.1002/ana.10798

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1. Ann Neurol. 2004 Jan;55(1):97-104.

Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p.

Stevanin G(1), Bouslam N, Thobois S, Azzedine H, Ravaux L, Boland A, Schalling M,
Broussolle E, Dürr A, Brice A.

Author information:
(1)INSERM U289, Federative Institute for Neuroscience Research (IFR-70), Paris.

Autosomal dominant cerebellar ataxias constitute one of the most clinically,
neuropathologically, and genetically heterogeneous groups of neurodegenerative
disorders. Approximately 50 to 80% of the families carry mutations in genes known
to be implicated in spinocerebellar ataxias (SCAs). Numerous loci (SCAn) also
have been mapped, often in single families, but the responsible genes have not
yet been identified. This suggests further genetic heterogeneity. We have
ascertained 18 subjects from a large French family in which cerebellar ataxia and
prominent sensory neuropathy segregated as a dominant trait. Intrafamilial
variability was high regarding age at onset (17 months to 39 years), severity,
and the clinical picture that ranged from pure sensory neuropathy with little
cerebellar involvement to a Friedreich’s ataxia-like phenotype. After excluding
known genes/loci responsible for SCA and hereditary sensory neuropathies, we
detected linkage with chromosome 2p markers in a genomewide screen. We designated
this new locus SCA25 after testing of 16 additional markers. Maximum two-point
logarithm of odds scores of 3.15 and 3.10 were obtained at D2S2378 and D2S2734,
respectively. Haplotype analysis defined a critical 12.6cM region of 15Mb between
D2S2174 and D2S2736. No linkage to this locus was found in four other families.
This interval contains several genes that could be responsible for the disease.
One of these genes, CRIPT, encodes a postsynaptic protein, but no mutations were
found by direct sequencing, excluding its responsibility in the disease. CAG
repeat expansions often are involved in SCA pathogenesis, but no pathological
expansions were found at the protein or at the DNA level using the 1C2 antibody
and the repeat expansion detection method, respectively. The gene responsible for
SCA25 remains to be identified.

DOI: 10.1002/ana.10798
PMID: 14705117 [Indexed for MEDLINE]

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