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A Simple Composite Phenotype Scoring System for Evaluating Mouse Models of Cerebellar Ataxia
Published on: May 21, 2010
Late onset hereditary episodic ataxia
1Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Neurologie, Paris, France.
Journal of Neurology, Neurosurgery, and Psychiatry
|April 18, 2009
Summary
This study describes a new form of late-onset episodic ataxia (EA) in a French family. Genetic analysis excluded known EA genes, suggesting a novel genetic cause for this progressive neurological disorder.
Area of Science:
- Neurogenetics
- Neurology
- Molecular Biology
Background:
- Episodic ataxias (EA) are rare hereditary neurological disorders characterized by recurrent episodes of ataxia.
- Significant clinical and genetic heterogeneity exists among EA types, with seven loci and four genes identified to date.
- Further investigation of familial and sporadic cases is crucial for a comprehensive understanding of EA's spectrum.
Observation:
- A two-generation French family presented with late-onset episodic ataxia, with symptom onset between 48 and 56 years.
- Affected individuals exhibited variable symptom severity, including daily attacks, progressive cerebellar ataxia, and poor response to acetazolamide.
- Brain MRI revealed cerebellar atrophy in affected members, indicated by a reduced cerebellar volume to total intracranial volume ratio.
Findings:
- Genetic analysis, including haplotype analysis and mutation screening of known EA genes (CACNA1A, EAAT1, KCNA1), did not identify any causative mutations.
- Known EA loci (EA2, EA5, EA6, EA7) were excluded, ruling out common genetic causes for this family's condition.
Implications:
- This study identifies a novel phenotype of episodic ataxia characterized by late onset and progressive cerebellar signs.
- The exclusion of known EA genes suggests the involvement of unidentified genetic factors, necessitating further research into the genetic basis of EA.
- Understanding the genetic underpinnings of this new EA phenotype may lead to improved diagnostics and targeted therapies for patients with hereditary ataxias.
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