Aspectos moleculares das ataxias espinocerebelares autossomicas recessivas




The spinocerebellar ataxia form a group of neurodegenerative disorders with clínical heterogeneity. They are characterized by cerebelIar dysfunction with progressive ataxia, incoordenation and dysarthria. Familial cases show variable pattem of inheritance: autossomal dominant (AD) or autossomal recessive (AR). To date, thereare four loci described for the spinocerebelIar ataxia with AR: Friedreich ataxia (F A) on chromosome 9q; ataxia with vitamin E deficiency (ADVE) on chromosome 8q, the lnfantile Onset SpinocerebelIar Ataxia (IOSCA) on chromosome 10q and ataxia telangiectasia on chromosome llq. the %25 gene. This gene encodes for a 210 aminoacids protein named Frataxin, with mitochondrial target. Normal (GAA)n alleles range ITom seven to 30 (GAA)n units and expanded (GAA)n alleles have 200 to 1700 (GAA)n units. ADVE is clinically identical to the FA,-and the best way to di:fferentiate between the two forms is by molecular testing. ADVE is caused by di:fferent types of mutations, found in the a-TTP gene, with codes for alpha tocopherol transfer protein, with 278 aminoacids. To date, there are 13 di:fferent mutations reported in a-TTP. We studied 97 individuais, belonging to 58 unrelated families. The ITequency of patients with FA mutation was 15% among our patients. No mutations were found in a-TTP gene by SSCP ana1ysis. This is the first report on the fTequency of different mutations causing spinocerebellar ataxia with AR inheritance in the Brazilian population. In addition, we analyzed the molecular characteristics of the mutations detected and performed genotype - phenotype correlation


vitamina e ataxia sistema nervoso - degeneração - doenças

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