The Diagnostic Genetics Subcommittee of Korean Association of External Quality Assessment Service conducted two trials in 2015 based on cytogenetics and molecular genetics surveys. A total of 43 laboratories participated in the chromosome surveys, 31 laboratories participated in the fluorescence in situ hybridization surveys, and 133 laboratories participated in the molecular genetics surveys. All except one laboratory showed acceptable results in the cytogenetics surveys. The molecular genetics surveys included the following tests: Mycobacterium tuberculosis detection, hepatitis B and C virus detection and quantification, human papilloma virus genotyping, gene rearrangement tests for leukaemias and lymphomas, genetic tests for JAK2, FMS-like tyrosine kinase 3, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2 ), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-Willi/Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome (FMR1), apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, ABO genotyping, cytochrome P450 2C9 genotyping, cytochrome P450 2C19 genotyping, and DNA sequencing analysis. The molecular genetics surveys showed excellent results for most of the participants. The external quality assessment program for genetics analysis in 2015 proved to be helpful for continuous education and the evaluation of quality improvement.
Achondroplasia ; Acidosis, Lactic ; Apolipoproteins ; Breast ; Cytochrome P-450 Enzyme System ; Cytogenetics ; Deafness ; Education ; Epilepsies, Myoclonic ; Fluorescence ; fms-Like Tyrosine Kinase 3 ; Fragile X Syndrome ; Gene Rearrangement ; Genetics* ; Hearing Loss ; Hepatitis B ; Hepatolenticular Degeneration ; Humans ; Huntington Disease ; In Situ Hybridization ; Korea* ; Li-Fraumeni Syndrome ; Lymphoma ; Methylenetetrahydrofolate Reductase (NADPH2) ; Molecular Biology ; Multiple Endocrine Neoplasia ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic ; Muscular Dystrophy, Duchenne ; Mycobacterium tuberculosis ; Optic Atrophy, Hereditary, Leber ; Ovarian Neoplasms ; Papilloma ; Quality Improvement ; Sequence Analysis, DNA ; Spinocerebellar Ataxias ; Stroke

PURPOSE: Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuron disease characterized by proximal muscle weakness, muscle atrophy, and fasciculation. Although SBMA is not uncommon in Korea, there is only one study reporting clinical characteristics and genotype-phenotype correlation in Korean patients. MATERIALS AND METHODS: In this study, age at the onset of symptoms, the score of severity assessed by impairment of activities of daily living milestones, and rate of disease progression, and their correlations with the number of CAG repeats in the androgen receptor (AR) gene, as well as possible correlations among clinical characteristics, were analyzed in 40 SBMA patients. RESULTS: The median ages at onset and at diagnosis were 44.5 and 52.5 years, respectively, and median interval between onset and diagnosis and median rate of disease progression were 5.0 years and 0.23 score/year, respectively. The median number of CAG repeats in the AR gene was 44 and the number of CAG repeats showed a significant inverse correlation with the age at onset of symptoms (r=-0.407, p=0.009). In addition, patients with early symptom onset had slower rate of disease progression. CONCLUSION: As a report with the largest and recent Korean cohort, this study demonstrates clinical features of Korean patients with SBMA and reaffirms the inverse correlation between the age at disease onset and the number of CAG repeats. Interestingly, this study shows a possibility that the rate of disease progression may be influenced by the age at onset of symptoms.
Activities of Daily Living ; Adult ; Age of Onset ; Asian Continental Ancestry Group/*genetics ; Bulbo-Spinal Atrophy, X-Linked/genetics/*physiopathology ; Disease Progression ; Female ; Genes, Recessive ; Genetic Association Studies ; Genotype ; Humans ; Male ; Middle Aged ; Muscle Weakness/*physiopathology ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic/*genetics ; Phenotype ; Receptors, Androgen/*genetics ; Republic of Korea ; Trinucleotide Repeats/genetics

Quality control for genetic tests has become more important as testing volume and clinical demands have increased dramatically. The diagnostic genetics subcommittee of Korean Association of External Quality Assessment Service conducted two trials in 2014 based on cytogenetics and molecular genetics surveys. A total of 44 laboratories participated in the chromosome surveys, 33 laboratories participated in the fl uorescence in situ hybridization (FISH) surveys, and 130 laboratories participated in the molecular genetics surveys as a part of these trials. All laboratories showed acceptable results in the chromosome and FISH surveys. The molecular genetics surveys included various tests: Mycobacterium tuberculosis detection, hepatitis B and C virus detection and quantification, human papilloma virus genotyping, gene rearrangement tests for leukaemia and lymphomas, genetic tests for JAK2, FMS-like tyrosine kinase 3, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke like episodes, myoclonic epilepsy ragged red fibre, Prader-Willi/Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome, nonsyndromic hearing loss and deafness (GJB2), multiple endocrine neoplasia 2 (RET), Leber hereditary optic neuropathy (major mutation), apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, ABO genotyping, and DNA sequencing analysis. Molecular genetic surveys showed excellent results for most of the participants. The external quality assessment program for genetic analysis in 2014 proved to be helpful for continuous education and the evaluation of quality improvement.
Achondroplasia ; Acidosis, Lactic ; Apolipoproteins ; Breast ; Cytogenetics ; Deafness ; Education ; Epilepsies, Myoclonic ; fms-Like Tyrosine Kinase 3 ; Fragile X Syndrome ; Gene Rearrangement ; Genetics* ; Hearing Loss ; Hepatitis B ; Hepatolenticular Degeneration ; Humans ; Huntington Disease ; In Situ Hybridization ; Korea ; Li-Fraumeni Syndrome ; Lymphoma ; Methylenetetrahydrofolate Reductase (NADPH2) ; Molecular Biology ; Molecular Diagnostic Techniques ; Multiple Endocrine Neoplasia ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic ; Muscular Dystrophy, Duchenne ; Mycobacterium tuberculosis ; Optic Atrophy, Hereditary, Leber ; Ovarian Neoplasms ; Papilloma ; Quality Assurance, Health Care ; Quality Control ; Quality Improvement ; Sequence Analysis, DNA ; Spinocerebellar Ataxias ; Stroke

Quality control for genetic tests has become more important as the test volume and clinical demands increase dramatically. The diagnostic genetics subcommittee of the Korean Association of Quality Assurance for Clinical Laboratories performed two trials for cytogenetics and molecular genetics surveys in 2013. A total of 43 laboratories participated in the cytogenetic surveys, 30 laboratories participated in the fluorescent in situ hybridization surveys, and 122 laboratories participated in the molecular genetics surveys in 2013. Almost all of them showed acceptable results. However, some laboratories had unacceptable results for karyotype nomenclature, detection of complex cytogenetic abnormalities in hematologic neoplasms and constitutional anomalies. The molecular genetics surveys included various tests: Mycobacterium tuberculosis detection, hepatitis B and C virus detection and quantification, human papilloma virus genotyping, gene rearrangement tests for leukaemia and lymphomas, genetic tests for JAK2, fms-related tyrosine kinase 3, Nucleophosmin, cancer-associated genes (KRAS, EGFR and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke like episodes, myoclonic epilepsy associated with ragged-red fibers, Prader-Willi/Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, Fragile X syndrome, non-syndromic hearing loss and deafness (GJB2), apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, ABO genotyping and DNA sequence analysis. Molecular genetic surveys showed excellent results for most of the participants. The external quality assessment program for genetic analysis in 2013 was proved to be helpful for continuous education and evaluation of quality improvement.
Achondroplasia ; Acidosis, Lactic ; Apolipoproteins ; Breast ; Chromosome Aberrations ; Cytogenetics ; Deafness ; Education ; Fragile X Syndrome ; Gene Rearrangement ; Genetics* ; Hearing Loss ; Hematologic Neoplasms ; Hepatitis B ; Hepatolenticular Degeneration ; Humans ; Huntington Disease ; In Situ Hybridization, Fluorescence ; Karyotype ; Korea ; Li-Fraumeni Syndrome ; Lymphoma ; MERRF Syndrome ; Methylenetetrahydrofolate Reductase (NADPH2) ; Molecular Biology ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic ; Muscular Dystrophy, Duchenne ; Mycobacterium tuberculosis ; Ovarian Neoplasms ; Papilloma ; Protein-Tyrosine Kinases ; Quality Control ; Quality Improvement ; Sequence Analysis, DNA ; Spinocerebellar Ataxias ; Stroke

I previously reported the PCR-based Spinal and bulbar muscular atrophy (SBMA) region polymorphisms in the three northeast Asian populations (Chinese, Koreans, Japanese) and Caucasians. Here I update this analysis by including the data of the allele distribution in 378 unrelated individuals from four populations in Asia. In this study I investigated PCR-based CAG repeat polymorphism on the SBMA locus among four Asian populations (Mongolian, Evenki, Orochon, Negrito) and performed the statistical analysis on the eight populations including the previously analyzed data. Both statistical analyses of one-way ANOVA (F=3.284, P=0.002) and Kruskal-Wallis test (chi-square=21.542, DF=7, P=0.003) showed remarkable differences in CAG allele distributions among the populations. Post-hoc test showed that the difference between Negritos and Caucasians was especially significant (Scheffe: P=0.042; Bonferroni: P=0.004). Also a significant differences among Northeast Asians, Caucasians and Negritos (Southeast Asian) were detected by these two tests (ANOVA; F=8.132, P.0.000, Kruskal-Wallis; chi-square=16.614, DF=2, P.0.000). Post-hoc test showed that the differences between Negritos and Caucasias was also especially significant (Scheffe: P=0.001; Bonferroni: P=0.000) among these three groups. These data present that the CAG repeat polymorphism of SBMA gene has a useful information for studies of human population genetics.
Alleles ; Asia ; Asian Continental Ancestry Group* ; Genetics, Population ; Humans ; Muscular Disorders, Atrophic* ; Trinucleotide Repeats*

The importance of quality control for dramatically growing genetic tests continues to be emphasized with increasing clinical demands. Diagnostic genetics subcommitee of KSQACP performed two trials for cytogenetic study in 2003. Cytogenetic surveys were performed by 33 laboratories and answered correctly in most laboratories except some problems in nomenclature and analysis for FISH and complex cytogenetic abnormalities in neoplasia. The molecular genetic test surveys include M. tuberculosis, HBV, HPV, leukemia/lymphoma, ApoE genotyping, Duchenne muscular dystrophy, myoclonic epilepsy and ragged red muscle fibers, and spinal and bulbar muscular atrophy. HPV, myoclonic epilepsy and ragged red muscle fibers, and spinal and bulbar muscular atrophy were the first challenge of the genetic survey. Molecular genetic survey showed excellent results in most participants, however, HPV tests should be improved by quality control in a few laboratories. External quality assessment program for cytogenetic analysis could be helpful to give participants many chances of continuous education and of interesting case materials.
Apolipoproteins E ; Chromosome Aberrations ; Cytogenetic Analysis ; Cytogenetics ; Education ; Epilepsies, Myoclonic ; Genetics* ; Korea* ; Molecular Biology ; Muscle Fibers, Slow-Twitch ; Muscular Disorders, Atrophic ; Muscular Dystrophy, Duchenne ; Quality Control ; Tuberculosis