Distribution of Alleles and Clinical Manifestation in Patients with Progressive Ataxia Caused by Trinucleotide Repeat Expansion / 대한진단검사의학회지

BACKGROUND: Trinucleotide repeat (TNR) expanded disorders represent a novel class of human mutations, which are characterized by abnormal elongation of the triplet repeat sequence in the human genome and is caused by heritable DNA instability. The aim of this study is to determine the relative frequency, distribution of alleles, and the clinical manifestation of TNR expanded disorders in Korean patients with progressive ataxia. METHODS: A total of 76 clinical specimens that were suspicous of hereditary cerebellar ataxia were submitted from January 1999 to August 2001 and tested for TNR expanded disorders by PCR analysis. RESULTS: Spinocerebellar ataxia (SCA) type 1 was the most common hereditary ataxia (5.3%), while SCA2, SCA3, SCA6, SCA7, and dentatorubral and pallidoluysian atrophy (DRPLA) represented 2.6%, 3.9%, 2.6%, 2.6%, and 1.3% of progressive ataxia patients, respectively. This result is different from previous reports concerning Caucasian, Chinese and Koreans. CONCLUSIONS: This study may provide the basis for the study of TNR expanded disorders in Korean patients. To elucidate the prevalence and frequencies of mutation types in Koreans, a large scale study should be performed.

CAG Repeats of KCNN3 Gene in the Patients with Schizophrenia / 신경정신의학

OBJECTS:We investigated a possible association between the polymorphic trinucleotide repeat(TNR) expansion in neuronal potassium channel gene KCNN3 and schizophrenia. METHODS: CAG/CTG repeat distribution in KCNN3, CTG18.1 and ERDA1 was examined and the copy number of ligation product in repeat expansion detection(RED) was measured in Korean patients with schizophrenia(n=245) and ethnically matched healthy controls(n=116). RESULTS: Longer alleles in the KCNN3 gene were over-represented in patients. The frequency of alleles with CAG repeats longer than 19 copy in the KCNN3 gene was higher in the patients with schizophrenia as compared to controls(73.3% vs. 65.1%;p=0.029, Fisher's exact test). And this difference was more prominent in schizophrenic patients with familial background(p=0.03, Fisher's exact test). We found no difference in the frequency of longer alleles between negative and positive subtypes of schizophrenia. Ligation product size in RED and alleles with CAG repeat number in the CTG18.1 gene was not increased in the patients. The copy number of ligation product in RED was highly correlated with CAG/CTG copies of ERDA1 in the patient group(r=0.45, p<0.001) as well as in the control group(r=0.44, p<0.001). However, CAG repeat length in the KCNN3 gene was not correlated with ERDA1 score. CONCLUSIONS: Our results support the hypothesis that the longer allele of KCNN3 may be considered as a candidate gene for schizophrenia, especially in the case with familial background. And the RED assay results was affected by the CAG copy number of ERDA1.