RESUMEN
Three patients from a previously described family with autosomal dominant chorea-acanthocytosis were found to have the CTG trinucleotide repeat expansion mutation of the junctophilin-3 gene associated with Huntington's disease-like 2 (HDL2). One of six previously identified patients with HDL2 had acanthocytosis on peripheral blood smear, suggesting that HDL2 should be considered in the differential of chorea-acanthocytosis.
Asunto(s)
Acantocitos/patología , Corea/genética , Corea/patología , Proteínas de la Membrana/genética , Expansión de Repetición de Trinucleótido , Acantocitos/química , Adolescente , Adulto , Edad de Inicio , Proteína 1 de Intercambio de Anión de Eritrocito/análisis , Trastornos de los Cromosomas , Análisis Mutacional de ADN , Diagnóstico Diferencial , Electroforesis en Gel de Poliacrilamida , Membrana Eritrocítica/química , Femenino , Genes Dominantes , Humanos , Enfermedad de Huntington/diagnóstico , Masculino , Persona de Mediana Edad , Mutación , Proteínas/genética , Proteínas de Transporte VesicularRESUMEN
BACKGROUND: The term chorea-acanthocytosis describes a heterogeneous group of neurodegenerative disorders with variable clinical features and modes of inheritance. The characteristic acanthocytic appearance of red blood cells is attributed to abnormalities of a membrane protein, band 3, although the relationship between this and the neurodegenerative process has yet to be determined. OBJECTIVE: To describe features of phenotype, inheritance, and neuropathological findings in a family with this disorder. METHODS: Clinical and hematologic evaluations were performed on all available family members and neuropathological examination was performed on one case. RESULTS: Autosomal dominant inheritance was evident, with variable clinical features of chorea or parkinsonism, marked cognitive changes, but no seizures or peripheral neurologic abnormalities. Abnormalities of band 3 were demonstrated on gel electrophoresis of red blood cell membranes. Neuropathological examination revealed severe neuronal loss of the caudate-putamen and intranuclear inclusion bodies in many areas of the cerebral cortex. These inclusion bodies were immunoreactive for ubiquitin, expanded polyglutamine repeats, and torsinA. CONCLUSIONS: This family extends the genetic spectrum of chorea-acanthocytosis to include autosomal dominant inheritance, possibly due to expanded trinucleotide repeats. Intraneuronal inclusion bodies have recently been associated with a wide range of inherited neurodegenerative disorders and may provide a clue to etiopathogenesis, in addition to potentially indicating a function of torsinA.