Incidence of Fragile X Syndrome in Korean Patients with Mental Retardation / 대한산부인과학회잡지

Fragile X syndrome is the most common cause of inherited mental retardation. It accounts for 0.2% - 2.7% of patients with mental retardation, based upon the molecular genetic diagnosis. However, the exact prevalence of fragile X syndrome in Korean patients with mental retardation is unknown. We have performed cytogenetic and molecular analysis for fragile X syndrome in 212 Korean patients with mental retardation. Among them, six patients (2.8%) was identified as carrying fragile X syndrome by both cytogenetic and molecular analysis. The results by cytogenetic analysis was identical to those by molecular analysis. Cytogenetic analysis of 6 carriers (mothers of patients with proven fragile X syndrome) showed a fragile X chromosome in one patients (16.7%) while molecular analysis revealed premutation in all patients. PCR method using Klentaq1 Pfu polymerase showed the same results as those by PCR method using Exo(-) Pfu polymerase, but the former method is recommended because of its simplicity in technical aspect. These data suggest that the prevalence of fragile X syndrome in Korean patients with mental retardation is 2.8%, not significantly different from those in Caucasians.

Homozygous Deletion of CDK4I in Acute Leukemia / 대한혈액학회지

BACKGROUND: The CDK4I (cyclin dependent kinase 4 inhibitor) gene is on the chromosome 9p21. It encodes p16, which binds to CDK4, and inhibits phosphorylation of retinoblastoma protein (pRb) by D-type cyclin-CDK4 complex. D-type cyclin-CDK4 complex phosphorylates pRb which regulates transition of G1 to S phase of the cell cycle. So inactivation of the CDK4I gene leads to the dysregulation of the cell cycle and may contribute to the malignant progression of cells. Homozygous deletion of CDK4I gene was frequently found in human hematologic malignancies. The purpose of this study is to find the relationship between the CDK4I gene homozygous deletion and diverse acute leukemia. METHODS: We analyzed homozygous deletions of the CDK4I gene from 21 cases of acute leukemia by means of Southern blot analysis (10 B-cell acute lymphocytic leukemias, 6 T-cell acute lymphocytic leukemias, 5 acute myelogenous leukemias). Hybridization of EcoRI digested DNA using CDK4I probes (exon 1 and exon 2) obtained by PCR of human control DNA was performed. RESULTS: 1) We observed 4 cases (19%) of homozygous deletions in 21 cases of acute leukemia. 2) ALL 4 cases of homozygous CDK4I deletion were T-cell ALL which accounted for 66% (4/6 cases) of T-cell ALLs. 3) Homozygous CDK4I deletions were not found in any cases of B-ALLs (0/10 cases) and AML (0/5 cases). 4) In 4 cases of homozygous deletion, consistent results were obtained by 2 different CDK4I probes (pv 336-bp probe, pv 142-bp probe). CONCLUSION: The high frequency of CDK4I homozygous deletions in T-ALLs supports that the inactivation of these genes plays an important role in the pathogenesis of T- ALL.

Diagnosis of Fragile X Syndrome and DMD by using DIG System / 대한산부인과학회잡지

The aim of this study was to develop a rapid and safe non-radioactive DIG DNA labeling and detection for Southern blot analysis for fragile X syndrome and Duchenne muscular dystrophy (DMD). Southern blot analysis is accurate test showing expression of the (CGG)n repeat and abnormal methylation pattern of CpG island in hagile X syndrome, and good confirmative secondary test in case of deletion in DMD. But in terms of test rapidity, these conventional radioactive Southern analysis may not be feasible for rapid screening of prenatal samples and at-risk populations to determine their status and to provide genetic counseling to their families. As an alternative radioactive Southern blotting, DIG DNA labeling and detection system does not require handling of radioactive material nor require learning any new technology. The complete procedure of labeling the DNA and hybridization to detection of the first visible signal can be compbsbed witbin 7 days. In addition, hybridization solutions containing labeled DNA can be reused several times after renewed denaturation.

Loss of Heterozygosity of Chromosome 17p in Brain Tumors

With the methods of restriction fragment length polymorphisms(RFLPs) and southern blot analysis, gene deletion of chromosome 17p in 16 cases of brain tumors, was investigated. There were 4 cases of glioblastoma multiforme, 1 case of anaplastic astrocytoma, 4 cases of low grade astrocytoma, 3 cases of oligodendroglioma, and 4 cases of meningioma. Among restriction fragment length polymorphism(RFLP) DNA located in chromosome 17p, p144D 6 and p SNZ 22 were imployed as the probes. In eight of 16 cases(50%) constitutional heterozygosity was observe dfor p144 D6 probe on the short arm of chromosome 17, and in nine of 16 cases(56%) for PYNZ 22.1 probe. With both probes constitutional heterozygosity was observed in thirteen of 16 cases(81%). And the loss of constitutional heterozygosity was detected in two of 14 informative cases. Although, with the malignant gliomas, including 4 cases of glioblastoma multiforme and 1 case of anaplastic astrocytoma, two of 4 informative cases showed loss of constitutional heterozygosty, None of 9 informative cases showed loss of heterozygosity with the other brain tumors(low grade astrocytoma, oligodendroglioma, and meningioma).