Clinical and neuroimaging study of spinocerebellar ataxia type 2

Abstract

Background Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant genetic disease characterized by cerebellar ataxia, ophthalmoplegia, slow saccade, hyporeflexia, action tremor, cognitive decline and peripheral neuropathy. The brain MRI shows obvious atrophy of cerebellum and brainstem, indicating typical change of olivopontocerebellar atrophy. SCA2 is caused by an expanded cytosine-adenine-guanine (CAG) trinucleotide repeat in the encoding region of ATXN2. The normal CAG repeats range from 13 to 31, and ataxic phenotype occurs when the repeats are more than 34. This study focused on the clinical and imaging features of 5 SCA2 families confirmed by genetic testing. The correlation between phenotype and genotype was analyzed. Methods The pathological CAG triplet repeat expansions of SCA1-3, 6, 7, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) genes were analyzed in the probands of 708 autosomal dominant SCA families and 119 sporadic SCA cases. The CAG repeat of ATXN2 gene was amplified by polymerase chain reaction (PCR) and agarose gel electrophoresis. Fragment analysis based on CEQ8000 sequencer were applied to analyze expanded alleles. Results Expanded CAG repeats of ATXN2 gene were detected in 45 probands of SCA2 families. Most of the patients manifested with the typical clinical features of SCA2 such as cerebellar ataxia, ophthalmoplegia, slow saccade and hyporeflexia. Some of them also associated with action tremor. The brain MRI showed obvious atrophy of cerebellum and brainstem. The correlation between clinical features and CAG repeat of ATXN2 gene was
studied carefully in 5 families. Conclusion Genetic analysis provides the basis for the diagnosis of SCA2. Clinical and neuroimaging features are very helpful in the diagnosis and differential diagnosis of this disease. For the identification of cases carrying intermediate allele, it is important to combine clinical, imaging features with dynamic mutation analysis in the affected cases within the family.