Two Huntington Department Of Clinical, Imaging Characteristics And Gene Mutation Analysis

Objective: To explore the clinical, neuroimaging features and identify mutations of IT15, DRPLA, JPH3 and TBP genes in a big Chinese family of Chorea (pedigree 1) and the clinical, neuroimaging features and identify mutations of IT15 gene in another big Chiese family of typical huntington's disease (pedigree 2). To reveal the pathogenesis of huntington's disease by mutation analysis.Methods: Five patients of pedigree 1 and three affected members of pedigree 2 were assessed according to their clinical and neuroimaging features. Genomic DNA of 18 family individuals from pedigree 1 was used for amplification of the CAG/CTG repeats of IT15, DRPLA, JPH3 and TBP genes by PCR. The numbers of CAG/CTG were determined by electrophoreses through an 8% denaturing polyacrylamide gel and sequence analysis. Genomic DNA of 24 family individuals from pedigree 2 was also used for amplification of the (CAG)_n repeats of IT15 gene by PCR; The numbers of CAG were directly determined by electrophoreses through a 6% polyacrylamide gel and sequence analysis. Results: In pedigree 1, the main symptoms of five patients were involuntary movements. MRI scans showed no obvious caudate atrophy in three patients. While the proband showed basal ganglia blood flow was reduced following SPECT scan. Total 9 out of 18 family members had more than 40 (CAG)_n repeats in the IT15 gene (5 patients and 4 asymptomatic), but no mutation was detected in the DRPLA, JPH3 and TBP genes in 18 family members. In pedigree 2, two affected family members have the typical clinical features of huntington's disease. An 18-year-old patient was onset with behavior abnormal. CT scans of the proband demonstrated significant caudate atrophy which resulting inenlargement of lateral ventricle. All the patients and 2 relatives in high risk had more than 50 (CAG)n repeats in the IT15 gene. The 18-year-old patient had an expanded (CAG)n allele of 70 repeats. In addition, no expansions in the IT15 gene was found in 19 family members. In these families, no obvious correlation existed between the number of (CAG)n repeats when the (CAG)n expansion was within 50 repeats, while there was a significant negative correlation between age onset of symptoms and the size of the expanded (CAG)n allele when the number of (CAG)n repeats was beyond 50. Conclusions: The (CAG)n expansion at the IT15 gene is the disease-causing mutation in the two Chinese families. HD cannot be made definite diagnosis on the basis of clinical and neuroimaging features. The (CAG)n expansion at the IT15 gene by mutation analysis can provide us valuable insights in HD. There was some correlation between age onset of symptoms and the size of the (CAG)n repeats.