Haplotype analysis encompassing HTT gene in Chinese patients with Huntington's disease.

BACKGROUND AND PURPOSE: Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder with varied prevalence in different populations, which may be associated with specific haplotypes. This study aimed to explore the haplotypes encompassing the HTT gene in the Chinese population. METHODS: A total of 406 individuals with HD and 59 normal relatives from 253 families with HD were enrolled. A total of 29 tag single nucleotide polymorphisms (tSNPs) were selected and genotyped for the haplotype analysis. RESULTS: In stage one, we used 18 tSNPs to replicate the distribution of three major haplogroups (A, B, C). We found that risk-associated haplogroup variants A1 and A2, enriched on Caucasian HD chromosomes, were totally absent from both Chinese HD and control chromosomes, and the distributions of haplogroups between HD and control chromosomes were similar. Therefore, in stage two, we used 29 tSNPs (including the18 tSNPs) to define new haplogroups (I, II, III) and found that haplogroup I accounted for 61.4% on HD chromosomes and 34.4% on control chromosomes, indicating that haplogroup I was enriched on Chinese HD chromosomes. CONCLUSIONS: This is the first haplotype analysis encompassing HTT in the Chinese population. The results contribute to explaining the low prevalence of HD in China and provide a better understanding of genetic diversity in the HTT region.

Chinese patients with Machado-Joseph disease presenting with complicated hereditary spastic paraplegia.

BACKGROUND AND PURPOSE: The clinical overlap between Machado-Joseph disease (MJD) and autosomal dominant complicated hereditary spastic paraplegia (AD-HSP) is extensive and the differentiation between them can be difficult on clinical ground. However, patients are seeking the right diagnosis and it is important for neurologists to distinguish them in the early stage. METHODS: In recent 10 years, we have recruited and followed-up three families which were initially diagnosed as complicated AD-HSP based on the clinical criteria. Mutation analyses of SPG4, SPG3A and ATXN3 were performed in the index cases. RESULTS: No mutations on SPG4 and SPG3A were found. Mutation analysis of ATXN3 showed that these cases have one expanded allele and one normal allele. The copy numbers of CAG repeats were 80/28, 86/28 and 83/33, respectively. CONCLUSIONS: The molecular diagnosis confirmed that they were MJD patients though they had been misdiagnosed as complicated AD-HSP for many years. The copy numbers of expanded allele were more than 80 and the copy numbers of normal allele were more than 27, which could somewhat explain the earlier onset age of these cases and the anticipation of the pedigrees. Our data emphasize the necessity to perform the mutation analysis of ATXN3 in clinically diagnosed complicated AD-HSP patients.