PURPOSE: X-linked agammaglobulinemia(XLA) is an immunodeficiency caused by abnormalities in Bruton's tyrosine kinase(Btk), and is characterized by a deficiency of peripheral blood B cells. We studied the cytoplasmic expression of Btk protein and analyzed the Btk gene in peripheral blood mononuclear cells from two siblings and one cousin with XLA, as well as additional family members. METHODS: Btk protein expression was analyzed by flow cytometry. Isolation of the coding sequence of the Btk gene was performed by amplification using the reverse transcription-polymerase chain reaction(RT-PCR) technique. Sequence alterations were screened by the single-stranded conformation polymorphism(SSCP) method and characterized by standard sequencing protocols. RESULTS: Cytoplasmic expression of Btk protein in monocytes was not detected in three patients with XLA. In addition, Btk protein analysis clearly showed cellular mosaicism in monocytes from four obligate carriers, findings further supported by SSCP. A single base pair mutation(T to C) in Btk-exon three, which encodes the PH domain, was identified in four XLA patients. A diagnostic sequencing analysis was established to detect heterozygotic pattern in 4 carrier females. Furthermore, we found significant clinical heterogeneity in individuals with the same gene mutation. CONCLUSION: The implicating genetic alteration provided valuable clues to the pathogenesis of XLA in Korea and the flow cytometric analysis was suggested as a useful tool for rapid detection of XLA patients and carriers. The present study has identified a genetic mutation in the Btk coding region and demonstrated heterogeneity in clinical manifestations among patients with the same mutation. A flow cytometric analysis was found to be informative in establishing a deficiency of Btk protein in both patients and carriers and is recommended as a frontline procedure in the molecular diagnosis and work-up of XLA.
Agammaglobulinemia* ; B-Lymphocytes ; Base Pairing ; Clinical Coding ; Cytoplasm ; Diagnosis ; Female ; Flow Cytometry ; Humans ; Hydrogen-Ion Concentration ; Korea ; Monocytes ; Mosaicism ; Polymorphism, Single-Stranded Conformational ; Population Characteristics ; Protein-Tyrosine Kinases* ; Siblings ; Tyrosine*

PURPOSE: This study was undertaken to evaluate the correlation between p53, bcl-2 expression and pathologic factors stage, anatomic location, histologic grade, gross pattern, lymph node metastasis of the colorectal cancer. METHODS: Analysis were made on archival pathology tissue of 56 patients with colorectal cancer. The oncoproteins were localized using commerically available monoclonal antibodies : DO-7 for, p53 and clone 124 for bcl-2. RESULTS: P53 protein was detected in 53 out of 56(94.6%) adenocarcinomas of the colorectal cancer and the most frequently expressed patterns of immunoreactivity of p53 were strong in intensity in 40 cases(71.4%) and were diffuse in pattern in 39 cases(69.6%). Bcl-2 protein was detected in 34 out of 56(60.7%) adenocarcinomas of the colorectal cancer and the most frequently expressed patterns of immunoreactivity of bcl-2 were weak in intensity in 17 cases(30.3%) and were diffuse in pattern in 16 cases(28.6%). There was no correlation between p53, bcl-2 expression and Dukes' stage, anatomic location ,histologic grade, gross pattern of tumor, lymph node metastasis of the colorectal cancer. CONCLUSION: 53 mutation and bcl-2 expression are frequent event in human colorectal carcinoma as shown in this study, but p53 and bcl-2 protein expression is not significant independent predicator of aggressiveness and progression of colorectal cancers.
Adenocarcinoma ; Antibodies, Monoclonal ; Clone Cells ; Colorectal Neoplasms* ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Oncogene Proteins ; Pathology

Krabbe disease is an autosomal recessive disorder involving white matter caused by deficient activity of the lysosomal galactocerebrosidase (GALC). A typical infantile-onset patient shows developmental regression, spasticity, and seizure before 6 months of age, and dies within 2 years. Previously, one case was confirmed by an enzyme test in Korea. We herein report a 2 year-old girl who showed the characteristic clinical course and neuroimaging features of infantile-onset Krabbe disease. Genetic testing identified the compound heterozygote mutations in the GALC gene; NLWE212_215TP/302A.
beta-Galactosidase* ; Child, Preschool ; Female ; Galactosylceramidase ; Genetic Testing ; Heterozygote ; Humans ; Korea ; Leukodystrophy, Globoid Cell* ; Muscle Spasticity ; Neuroimaging ; Seizures