RESUMO
OBJECTIVE: To describe reduced penetrance associated with early onset in a Brazilian family with spinocerebellar ataxia type 10. DESIGN: Clinical examination and molecular analysis for the ATTCT repeat responsible for spinocerebellar ataxia type 10 in a patient and family members through 3 generations. SETTING: Ambulatory care. Patients A 28-year-old female Brazilian patient who presented with early-onset cerebellar ataxia and epilepsy, and her 9 asymptomatic relatives. Main Outcome Measure Genotype-phenotype correlation. RESULTS: Molecular testing on this patient showed an expansion of approximately 850 ATTCT repeats at the SCA10 locus. Similar SCA10 expansions of approximately 850 repeats were identified in 6 of 8 asymptomatic paternal relatives examined. CONCLUSION: The stably transmitted pentanucleotide expansion of approximately 850 repeats may represent a mutant SCA10 allele with reduced penetrance that may express an early-onset, severe phenotype.
Assuntos
Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/genética , Adulto , Ataxina-10 , Brasil , Saúde da Família , Feminino , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Linhagem , Penetrância , Fenótipo , Ataxias Espinocerebelares/patologiaRESUMO
Dominant ataxias show wide geographic variation. We analyzed 108 dominant families and 123 sporadic ataxia patients from Mexico for mutations causing SCA1-3, 6-8, 10, 12, 17 and DRPLA. Only 18.5% of dominant families remained undiagnosed; SCA2 accounted for half (45.4%), followed by SCA10 (13.9%), SCA3 (12%), SCA7 (7.4%), and SCA17 (2.8%). None had SCA1, 6, 8, 12 or DRPLA. Among sporadic cases, 6 had SCA2 (4.9%), and 2 had SCA17 (1.6%). In the SCA2 patients we identified 6 individuals with the rare (CAG)(33) allele, 2 of whom showed early onset ataxia. The distribution of dominant ataxia mutations in Mexicans is distinct from other populations.