RESUMO
SCA12 is an autosomal dominant cerebellar ataxia characterized by onset in the fourth decade of life with action tremor of arms and head, mild ataxia, dysmetria, and hyperreflexia. The disease is caused by an expansion of >or=51 CAGs in the 5' region of the brain- specific phosphatase 2 regulatory subunit B-beta isoform (PPP2R2B) gene. SCA12 is very rare, except for a single ethnic group in India. We screened 159 Italian ataxic patients for SCA12 and identified two families that segregated an expanded allele of 57 to 58 CAGs, sharing a common haplotype. The age at onset, phenotype, and variability of symptoms were compatible with known cases. In one family, the disease was apparently sporadic due to possible incomplete penetrance and/or late age at onset. Our data indicate that SCA12 is also present in Italian patients, and its genetic testing should be applied to both sporadic and familial ataxias.
Assuntos
Ataxia/fisiopatologia , Proteínas do Tecido Nervoso/genética , Proteína Fosfatase 2/genética , Ataxias Espinocerebelares/diagnóstico , Expansão das Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Idoso , Saúde da Família , Feminino , Humanos , Itália , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prótons , Estudos Retrospectivos , Ataxias Espinocerebelares/genética , Adulto JovemRESUMO
Large expansions in the SCA2 and SCA7 genes (>100 CAG repeats) have been associated with juvenile and infantile forms of cerebellar ataxias that cannot be detected using standard polymerase chain reaction (PCR). Here, we describe a successful application of the fluorescent short tandem repeat-primed PCR method for accurate identification of these expanded repeats. The test is robust, reliable, and inexpensive and can be used to screen large series of patients, although it cannot give a precise evaluation of the size of the expansion. This test may be of practical value in prenatal diagnoses offered to affected or pre-symptomatic at-risk parents, in which a very large expansion inherited from one of the parents can be missed in the fetus by standard PCR.
Assuntos
Proteínas do Tecido Nervoso/genética , Reação em Cadeia da Polimerase/métodos , Degenerações Espinocerebelares/diagnóstico , Expansão das Repetições de Trinucleotídeos/genética , Ataxina-7 , Ataxinas , Estudos de Casos e Controles , Fluorescência , Triagem de Portadores Genéticos , Testes Genéticos , Humanos , Proteínas do Tecido Nervoso/metabolismo , Degenerações Espinocerebelares/genéticaRESUMO
Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative disorders, six of which are caused by expansion of a polyglutamine-coding CAG repeats ( SCA1- 3, 6, 7 and 17). In addition, expansions of a CAG triplet in the 5' region of a gene and a CTG triplet in an antisense RNA have been demonstrated in the SCA12 and SCA8 genes respectively. Our series of 134 ataxic patients (22 familial and 112 sporadic, tested negative for SCAI-3, 6, 7) was investigated for the presence of triplet expansions in the SCA8 and SCA12 genes. No SCA12 expansion was identified. A moderate SCA8 expansion (85-97 repeats) was found in two unrelated families with slowly progressive cerebellar ataxia. The frequency of SCA8 expansion accounts for approximately 4.3 % of the whole pool of our ataxia families (2 out of 46), while none of the 127 controls screened carried > 35 CTG+CTA repeats. Our data suggest a possible pathogenetic role of this mutation, which at present is still controversial, and confirm the rarity of the SCA12 expansion in Italian patients.
