title: Exome sequencing in familial corticobasal degeneration.
abstract: BACKGROUND
  Corticobasal degeneration (CBD) is a neurodegenerative, sporadic disorder of unknown cause. Few familial cases have been described.
  
  
  OBJECTIVE
  We aim to characterize the clinical, imaging, pathological and genetic features of two familial cases of CBD.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Corticobasal degeneration can have a familial presentation; the role of MRS2 and ZHX2 gene products in CBD should be further investigated.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX, USA. Electronic address: robertfekete@hotmail.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Fekete
authors.forename: Matthew
authors.initials: M
authors.lastname: Bainbridge
authors.forename: Jose Fidel
authors.initials: JF
authors.lastname: Baizabal-Carvallo
authors.forename: Andreana
authors.initials: A
authors.lastname: Rivera
authors.forename: Bradley
authors.initials: B
authors.lastname: Miller
authors.forename: Peicheng
authors.initials: P
authors.lastname: Du
authors.forename: Vladyslav
authors.initials: V
authors.lastname: Kholodovych
authors.forename: Suzanne
authors.initials: S
authors.lastname: Powell
authors.forename: William
authors.initials: W
authors.lastname: Ondo
mesh_terms: D000368:Aged; D001480:Basal Ganglia Diseases / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D017422:Sequence Analysis, DNA
keywords: Apraxia; Corticobasal degeneration; Corticobasal syndrome; Genetics; Progressive supranuclear palsy