S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Master's Degree_의학과)
SCA17의 경계값에 대한 연구
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2015. 2. 전범석.
- Background: SCA17 is an autosomal dominant cerebellar ataxia with expansion of CAG/CAA trinucleotide repeats in TATA-binding protein (TBP) gene. SCA17 can present with various clinical presentation including parkinsonism, ataxia, chorea and dystonia. SCA17 is diagnosed with detection of expanded CAG repeats in TBP, but reported pathologic repeat numbers as low as 41 overlap with reported normal repeat numbers.
Methods: Subjects included those with involuntary movement disorders including cerebellar ataxia, parkinsonism, chorea and dystonia who visited Seoul National University Hospital between Jan, 2006 and Apr 2014 and who were screened for SCA17. Those who were diagnosed with other genetic diseases or nondegenerative diseases were excluded. DNA from the healthy subjects who did not have a family history of parkinsonism, ataxia, psychiatric symptoms, chorea or dystonia served as a control. Total 5242 chromosomes from 2099 patients and 522 normal controls were analyzed.
Results: Total number of patients included in the analysis was 2099 (parkinsonism, 1706
and dystonia, 11) In normal control, up to 44 repeats were found. In 44 repeats, there were 7 (0.33%) patients and 1 (0.19%) normal control. In 43 repeats, there were 8 (0.38%) patients and 2 (0.38%) normal controls. In 42 repeats, there were 16 (0.76%) patients and 3 (0.57%) normal controls. In 41 repeats, there were 48 (2.29%) patients and 8 (1.53%) normal controls. Considering overlaps and non-significant differences of allelic frequencies between patients with normal controls in low-expansions, we couldnt locate the definite cut off value of SCA17.
Conclusions: As statistical analysis between normal control and patients in low expansions has failed to show difference so far, we must consider that clinical cases with low expansions could be idiopathic movement disorders showing coincidential CAG/CAA expansions. Thus we need to reconsider pathologic role of low-expansions(41-42). Long term follow up observation and comprehensive investigations using autopsy and imaging studies in patients and controls with low expansion are necessary to resolve the blurred cut off value of SCA17.