Huntington's disease phenocopies are clinically and genetically heterogeneous |
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Authors: | Edward J. Wild MRCP Ese E. Mudanohwo BSc Mary G. Sweeney BSc Susanne A. Schneider MD Jon Beck PhD Kailash P. Bhatia FRCP MD Martin N. Rossor FRCP MD Mary B. Davis FRCPath PhD Sarah J. Tabrizi FRCP PhD |
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Affiliation: | 1. Department of Neurodegenerative Disease, UCL Institute of Neurology/National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom;2. Edward J. Wild and Ese E. Mudanohwo contributed equally to this work as first authors.;3. Neurogenetics Unit, UCL Institute of Neurology/National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom;4. Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology/National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom |
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Abstract: | Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD‐like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD‐like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral‐pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty‐five patients with syndromes consistent with HD, who were HD expansion‐negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. © 2008 Movement Disorder Society |
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Keywords: | Huntington's disease (HD) phenocopies SCA17 familial prion disease HDL1 HDL2 |
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