Exome sequencing in familial corticobasal degeneration |
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Authors: | Robert Fekete Matthew Bainbridge Jose Fidel Baizabal-Carvallo Andreana Rivera Bradley Miller Peicheng Du Vladyslav Kholodovych Suzanne Powell William Ondo |
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Institution: | 1. Department of Neurology, Baylor College of Medicine, Houston, TX, USA;2. Department of Genetics, Baylor College of Medicine, Houston, TX, USA;3. The Methodist Hospital, Houston, TX, USA;4. Texas Tech University Health Sciences Center, Lubbock, TX, USA;5. IST High Performance & Research Computing, University of Medicine and Dentistry of NJ, Newark, NJ, USA;6. University of Texas Health Science Center at Houston, Houston, TX, USA |
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Abstract: | BackgroundCorticobasal degeneration (CBD) is a neurodegenerative, sporadic disorder of unknown cause. Few familial cases have been described.ObjectiveWe aim to characterize the clinical, imaging, pathological and genetic features of two familial cases of CBD.MethodsWe describe two first cousins with CBD associated with atypical MRI findings. We performed exome sequencing in both subjects and in an unaffected first cousin of similar age.ResultsThe cases include a 79-year-old woman and a 72-year-old man of Native American and British origin. The onset of the neurological manifestations was 74 and 68 years respectively. Both patients presented with a combination of asymmetric parkinsonism, apraxia, myoclonic tremor, cortical sensory syndrome, and gait disturbance. The female subject developed left side fixed dystonia. The manifestations were unresponsive to high doses of levodopa in both cases. Extensive bilateral T1-W hyperintensities and T2-W hypointensities in basal ganglia and thalamus were observed in the female patient; whereas these findings were more subtle in the male subject. Postmortem examination of both patients was consistent with corticobasal degeneration; the female patient had additional findings consistent with mild Alzheimer's disease. No Lewy bodies were found in either case. Exome sequencing showed mutations leading to possible structural changes in MRS2 and ZHX2 genes, which appear to have the same upstream regulator miR-4277.ConclusionsCorticobasal degeneration can have a familial presentation; the role of MRS2 and ZHX2 gene products in CBD should be further investigated. |
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Keywords: | Corticobasal degeneration Corticobasal syndrome Apraxia Genetics Progressive supranuclear palsy |
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