RESUMO
BACKGROUND: Spinocerebellar ataxias (SCA) are a group of rare hereditary neurodegenerative disorders. Rare cases of two SCA mutations in the same individual have been reported in the literature, however, family descriptions are lacking. AIMS: To characterize a family with combined SCA2 and SCA10 mutations. MATERIALS & METHODS: Analysis of the clinical features and genetic findings of a Bolivian family expressing both SCA2 and SCA10 mutations. RESULTS: The index case and his mother had both SCA2 and SCA10 mutations with a combined clinical phenotype of both disorders, including slow saccades (SCA2) and seizures (SCA10). The uncle of the index case had only an SCA10 mutation. DISCUSSION: Although the presence of two SCA mutations in the same individuals may be coincidental, the low probability of having both mutations suggests that these mutations might be particularly prevalent in Bolivian population. CONCLUSION: This is the first description of a family with two SCA mutations with affected subjects having a combined SCA2 and SCA10 phenotype.
Assuntos
Ataxina-10/genética , Ataxina-2/genética , Ataxias Espinocerebelares/genética , Bolívia , Expansão das Repetições de DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , FenótipoRESUMO
Spinocerebellar ataxia type 10 is an autosomal dominant neurodegenerative disorder. It was initially described in Mexican families presenting with ataxia and epilepsy, with or without polyneuropathy, pyramidal signs and cognitive symptoms. The authors report three patients from the same family who were asymptomatic until gestation and puerperium, when they developed symptoms and signs suggestive of the syndrome. Genetic diagnosis was made in the three patients. The authors hypothesize that hormonal changes are likely to influence the manifestation of the condition.
Assuntos
Complicações na Gravidez/diagnóstico , Complicações na Gravidez/genética , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Adulto , Idade de Início , Ataxina-10 , Feminino , Predisposição Genética para Doença , Humanos , Proteínas do Tecido Nervoso/genética , Linhagem , Período Pós-Parto , Gravidez , Complicações na Gravidez/fisiopatologia , Ataxias Espinocerebelares/fisiopatologiaAssuntos
Doenças dos Gânglios da Base/etnologia , Doenças dos Gânglios da Base/genética , Predisposição Genética para Doença/genética , Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/etnologia , Ataxias Espinocerebelares/genética , Adulto , Idoso , Argentina/etnologia , Ataxina-10 , Gânglios da Base/fisiopatologia , Doenças dos Gânglios da Base/fisiopatologia , Cerebelo/fisiopatologia , Análise Mutacional de DNA , Feminino , Frequência do Gene , Marcadores Genéticos , Testes Genéticos , Humanos , Indígenas Sul-Americanos/etnologia , Indígenas Sul-Americanos/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linhagem , Ataxias Espinocerebelares/fisiopatologia , População Branca/etnologia , População Branca/genéticaAssuntos
Alelos , Epilepsia/genética , Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/genética , Repetições de Trinucleotídeos , Idoso , Idoso de 80 Anos ou mais , Ataxina-10 , Southern Blotting , Brasil , Epilepsia/etnologia , Feminino , Humanos , Indígenas Sul-Americanos/genética , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Portugal/etnologia , Ataxias Espinocerebelares/etnologia , População Branca/genéticaRESUMO
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant ataxia caused by an ATTCT repeat expansion in an intron of the SCA10 gene. SCA10 has been reported only in Mexican families, in which the disease showed a combination of cerebellar ataxia and epilepsy. The authors report 28 SCA10 patients from five new Brazilian families. All 28 patients showed cerebellar ataxia without epilepsy, suggesting that the phenotypic expression of the SCA10 mutation differs between Brazilian and Mexican families.
Assuntos
Epilepsia/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia , Adulto , Fatores Etários , Idade de Início , Antecipação Genética/genética , Ataxina-10 , Brasil/epidemiologia , Criança , Comorbidade , Análise Mutacional de DNA , Epilepsia/epidemiologia , Feminino , Frequência do Gene , Testes Genéticos , Genótipo , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Linhagem , Fenótipo , Ataxias Espinocerebelares/epidemiologia , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused by expansion of an unstable ATTCT repeat. SCA10 has been described as a pure cerebellar syndrome accompanied by seizures and has been recognized only in families of Mexican origin. We describe clinical and molecular findings of 18 patients in four Mexican families with SCA10. Affected individuals had an average age at onset of 26.7 years (range 14-44 years) and ATTCT repeats ranging from 920 to 4,140 repeats. We could not detect significant anticipation or correlation between repeat size and age at onset, probably due to the small sample size. In addition to pure cerebellar ataxia and seizures, patients often showed soft pyramidal signs, ocular dyskinesia, cognitive impairment, and/or behavioral disturbances. Brain magnetic resonance imaging showed predominant cerebellar atrophy, and nerve conduction studies indicated polyneuropathy in 66% of patients. One family showed hepatic, cardiac, and hematological abnormalities in affected members. These findings suggest that a wide range of tissues may be affected in SCA10, including those outside of the cerebellum and cerebral cortex.