Spinocerebellar ataxia type 36 in the Han Chinese.
OBJECTIVE
To ascertain the genetic and clinical characteristics of the GGCCTG hexanucleotide repeat expansion in the nucleolar protein 56 gene (NOP56) in patients with spinocerebellar ataxia (SCA), sporadic ataxia, or amyotrophic lateral sclerosis (ALS) in Taiwan.


METHODS
We conducted clinical and molecular genetic studies of 109 probands with molecularly unassigned SCA from 512 SCA pedigrees, 323 healthy controls, 502 patients with sporadic ataxia syndromes, and 144 patients with ALS. Repeat-primed PCR assays and PCR-fragment analysis for the number of short hexanucleotide repeats (<40 units) were performed to ascertain NOP56 hexanucleotide repeat expansion. Genotyping included 8 microsatellite markers and 17 single nucleotide polymorphisms flanking NOP56 and covering a region of 1.8 Mb to assess a possible founder effect.


RESULTS
Eleven individuals from 3 SCA pedigrees have the NOP56 repeat expansions. The 3 pedigrees share a common haplotype spanning 5.3 kb flanking the NOP56 repeat expansions, suggesting a founder effect of spinocerebellar ataxia type 36 (SCA36) in the Han Chinese. The average age at symptom onset was 44.8 ± 3.8 years with truncal ataxia as the initial manifestation. Common features included slowly progressive truncal/limb ataxia, dysarthria, generalized hyperreflexia, and hearing impairment. Evidence of lower motor neuron involvement, including atrophy and fasciculation in the limb muscles and tongue, was mostly found in patients with prolonged disease duration. NOP56 repeat expansion was not detected in controls or patients with sporadic ataxic syndromes or ALS.


CONCLUSIONS
SCA36 is an uncommon subtype, which accounted for 0.6% (3/512) of SCA cases in the Han Chinese population.
Department of Neurology (Y.-C. Lee, C.-T.H., G.-T.L., Y.-C. Liao, B.-W.S.), Taipei Veterans General Hospital, Taiwan; Department of Neurology (Y.-C. Lee, P.-C.T., Y.-C. Liao, B.-W.S.), Institute of Clinical Medicine (Y.-C.G.), and Brain Research Center (Y.-C. Lee, P.-C.T., B.-W.S.), National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Neurology (Y.-C.G.), and School of Medicine (Y.-C.G.), College of Medicine, China Medical University, Taichung, Taiwan.
Yi-Chung
YC
Lee
Department of Neurology (Y.-C. Lee, C.-T.H., G.-T.L., Y.-C. Liao, B.-W.S.), Taipei Veterans General Hospital, Taiwan; Department of Neurology (Y.-C. Lee, P.-C.T., Y.-C. Liao, B.-W.S.), Institute of Clinical Medicine (Y.-C.G.), and Brain Research Center (Y.-C. Lee, P.-C.T., B.-W.S.), National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Neurology (Y.-C.G.), and School of Medicine (Y.-C.G.), College of Medicine, China Medical University, Taichung, Taiwan.
Pei-Chien
PC
Tsai
Department of Neurology (Y.-C. Lee, C.-T.H., G.-T.L., Y.-C. Liao, B.-W.S.), Taipei Veterans General Hospital, Taiwan; Department of Neurology (Y.-C. Lee, P.-C.T., Y.-C. Liao, B.-W.S.), Institute of Clinical Medicine (Y.-C.G.), and Brain Research Center (Y.-C. Lee, P.-C.T., B.-W.S.), National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Neurology (Y.-C.G.), and School of Medicine (Y.-C.G.), College of Medicine, China Medical University, Taichung, Taiwan.
Yuh-Cherng
YC
Guo
Department of Neurology (Y.-C. Lee, C.-T.H., G.-T.L., Y.-C. Liao, B.-W.S.), Taipei Veterans General Hospital, Taiwan; Department of Neurology (Y.-C. Lee, P.-C.T., Y.-C. Liao, B.-W.S.), Institute of Clinical Medicine (Y.-C.G.), and Brain Research Center (Y.-C. Lee, P.-C.T., B.-W.S.), National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Neurology (Y.-C.G.), and School of Medicine (Y.-C.G.), College of Medicine, China Medical University, Taichung, Taiwan.
Cheng-Tsung
CT
Hsiao
Department of Neurology (Y.-C. Lee, C.-T.H., G.-T.L., Y.-C. Liao, B.-W.S.), Taipei Veterans General Hospital, Taiwan; Department of Neurology (Y.-C. Lee, P.-C.T., Y.-C. Liao, B.-W.S.), Institute of Clinical Medicine (Y.-C.G.), and Brain Research Center (Y.-C. Lee, P.-C.T., B.-W.S.), National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Neurology (Y.-C.G.), and School of Medicine (Y.-C.G.), College of Medicine, China Medical University, Taichung, Taiwan.
Guan-Ting
GT
Liu
Department of Neurology (Y.-C. Lee, C.-T.H., G.-T.L., Y.-C. Liao, B.-W.S.), Taipei Veterans General Hospital, Taiwan; Department of Neurology (Y.-C. Lee, P.-C.T., Y.-C. Liao, B.-W.S.), Institute of Clinical Medicine (Y.-C.G.), and Brain Research Center (Y.-C. Lee, P.-C.T., B.-W.S.), National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Neurology (Y.-C.G.), and School of Medicine (Y.-C.G.), College of Medicine, China Medical University, Taichung, Taiwan.
Yi-Chu
YC
Liao
Department of Neurology (Y.-C. Lee, C.-T.H., G.-T.L., Y.-C. Liao, B.-W.S.), Taipei Veterans General Hospital, Taiwan; Department of Neurology (Y.-C. Lee, P.-C.T., Y.-C. Liao, B.-W.S.), Institute of Clinical Medicine (Y.-C.G.), and Brain Research Center (Y.-C. Lee, P.-C.T., B.-W.S.), National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Neurology (Y.-C.G.), and School of Medicine (Y.-C.G.), College of Medicine, China Medical University, Taichung, Taiwan.
Bing-Wen
BW
Soong