Analysis of trinucleotide repeats in different SCA loci in spinocerebellar ataxia patients and in normal population of Taiwan.
OBJECTIVE
To identify various subtypes of spinocerebellar ataxias (SCAs) among autosomal dominant cerebellar ataxia (ADCA) patients referred to our research center, SCA1, SCA2, SCA3/MJD (Machado-Joseph disease), SCA6, SCA7, SCA8 and SCA12 loci were assessed for expansion of trinucleotide repeats.


METHODS
A total of 211 ADCA patients, including 202 patients with dominantly inherited ataxia from 81 Taiwanese families and nine patients with sporadic ataxia, were included in this study and subjected to polymerase chain reaction (PCR) analysis. The amplified products of all loci were analyzed on both 3% agarose gels and 6% denaturing urea-polyacrylamide gels. PCR-based Southern blots were also applied for the detection of SCA7 locus.


RESULTS
The SCA1 mutation was detected in six affected individuals from one family (1.2%) with expanded alleles of 50-53 CAG repeats. Fourteen individuals from nine families (11%) had a CAG trinucleotide repeat expansion at the SCA2 locus, while affected SCA2 alleles have 34-49 CAG repeats. The SCA3/MJD CAG trinucleotide repeat expansion in 60 affected individuals from 26 families (32%) was expanded to 71-85 CAG repeats. As for the SCA7 locus, there were two affected individuals from one family (1.2%) possessed 41 and 100 CAG repeats, respectively. However, we did not detect expansion in the SCA6, SCA8 and SCA12 loci in any patient.


CONCLUSIONS
The SCA3/MJD CAG expansion was the most frequent mutation among the SCA patients. The relative prevalence of SCA3/MJD in Taiwan was higher than that of SCA2, SCA1 and SCA7.
Tsai
H-F
HF
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
Liu
C-S
CS
Leu
T-M
TM
Wen
F-C
FC
Lin
S-J
SJ
Liu
C-C
CC
Yang
D-K
DK
Li
C
C
Hsieh
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D000067696:Ataxin-1; D000067699:Ataxin-3; D000067719:Ataxin-7; D000067528:Ataxins; D015139:Blotting, Southern; D015220:Calcium Channels / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012016:Reference Values; D012097:Repressor Proteins; D020754:Spinocerebellar Ataxias / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D013624:Taiwan; D018911:Trinucleotide Repeats / Q000235:genetics*; D020864:Calcium Channels, N-Type
D000067696:Ataxin-1; D000067699:Ataxin-3; D000067719:Ataxin-7; D000067528:Ataxins; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C000593749:ATXN1 protein, human; C000593829:ATXN7 protein, human; C415906:ATXN8OS gene product, human; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C092341:ATXN3 protein, human