• Clinical and Experimental Pediatrics
• /
• v.45 no.2
• /
• pp.232-239
• /
• 2002

Purpose : Renal cystic diseases comprise a mixed group of heritable, developmental and acquired disorders. Recently the use of imaging modalities such as ultrasonography and radionuclide scanning has increased the detection rate of renal cystic diseases. We studied to review the clinical features and treatment of renal cystic diseases in children. Methods : This study was performed in 95 children with renal cystic diseases in the Department of Pediatrics, Asan Medical Center from October 1989 to June 2001. Results : In 95 patients, there were 55 cases(58.0%) with multicystic dysplastic kidney(MCDK), 19 cases(20.0%) with simple renal cysts, 13 cases(13.7%) with hereditary polycystic kidney diseases( 7 with autosomal recessive type, 5 with autosomal dominant type, 1 with undetermined), 6 cases(6.3%) with renal cysts in tuberous sclerosis and 1 case(1.0%) with medullary cystic disease. All MCDK patients had no renal dysfunction and hypertension during the follow-up period. Three out of 13 with polycystic kidney diseases had progressed to end-stage renal disease during the follow-up period. One case with a simple cyst underwent laparoscopic malsupialization for decompression. Conclusion : Renal cystic diseases have diverse clinicopathologic features and variable prognosis. We emphasize that routine follow-up should be performed to prevent and to detect early treatable complication in renal cystic diseases. Therefore, their natural history and treatment need further investigation and long term follow-up is required.

• Journal of Genetic Medicine
• /
• v.8 no.2
• /
• pp.100-104
• /
• 2011

Genetic testing has been generalized for the diagnosis of diseases and is an important method of research with advances in the life sciences. In particular, we should give better attention to the genetic test for a fetus. Because the fetus has no autonomy, ethical and social issues can arise. Therefore, appropriate genetic counseling is needed for parents to be informed with the characteristics, natural progress, and possible treatment of a genetic disease, prior to the prenatal genetic test. Physicians should also inform parents how a particular genetic risk factor relates with the likelihood of a disease, in order to assist the parents in making the best decision. Furthermore, the current law for prenatal genetic testing should be approached rationally.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.20 no.1
• /
• pp.24-28
• /
• 2020

Type III Glycogen storage disease (Type III GSD, OMIM#232400) is a genetic metabolic disorder in which undigested glycogen accumulates in the organs due to lack of glycogen debranching enzyme caused by AGL mutation. The clinical symptoms of type III GSD include hepatomegaly, delayed growth, hypoglycemia and muscle weakness. These clinical symptoms are similar to those of other types of GSD, making it difficult to distinguish clinically. The authors report a case of type III GSD diagnosed by gene panel sequencing. A 11-month old male patient was presented with hepatomegaly. In liver biopsy, glycogen was accumulated in hepatocytes, suggesting GSDs. For differential diagnosis of types of GSD, gene panel sequencing for GSDs was performed. As a result, two novel pathogenic compound heterozygous variants: c.311_312del (p.His104Argfs*15) and c.3314+1G>A in AGL were detected and the patient was diagnosed as type III GSD. After diagnosis, he started dietary treatment with cornstarch, and has been free from complications. After two years, two same variants were also identified in the chorionic villous sampling of the pregnant mother, and the fetus was diagnosed as type III GSD. Gene panel sequencing is useful for diagnosis of disease which is indistinguishable by clinically and has high genetic heterogeneity, such as GSD. After diagnosis, familial genetic analysis can provide adequate genetic counseling and rapid diagnosis.

• Journal of Genetic Medicine
• /
• v.7 no.2
• /
• pp.111-118
• /
• 2010

Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.

• Clinical and Experimental Pediatrics
• /
• v.45 no.9
• /
• pp.1126-1133
• /
• 2002

Purpose : Prader-Willi syndrome(PWS) is a complex disorder affecting multisystems with characteristic clinical features. Its genetic basis is an expression defect in the paternally derived chromosome 15q11-q13. We analyzed the clinical features and genetic basis of PWS patients for early detection and treatment. Methods : We retrospectively studied 24 patients with PWS in Department of Pediatrics, Samsung Medical Center, from September 1997 to September 2001. We performed cytogenetic and molecular genetic techniques using high resolution GTG banding techniques, fluorescent in situ hybridization and methylation-specific PCR for CpG island of SNRPN gene region. Results : The average birth weight of PWS patients was $2.67{\pm}0.47kg$ and median age at diagnosis was 1.3 years. The average height and weight of PWS patients under one year at diagnostic time were located in a 3-10 percentile relatively, and a rapid weight gain was seen between two and six years. Feeding problems in infancy and neonatal hypotonia were the two most consistently positive major criteria in over 95% of the patients. In 18 of the 24 cases(75%), deletion of chromosome 15q11-q13 was demonstrated and one case among 18 had an unbalanced 14;15 translocation. In four cases without any cytogenetic abnormality, it may be considered as maternal uniparental disomy and the rest showed another findings. Conclusion : We suggest diagnostic testing for PWS in all infants/neonates with unexplained feeding problems and hypotonia. It is necessary for clinically suspicious patients to undergo an early genetic test. As the genetic basis of PWS was heterogenous and complex, further study is required.

• Clinical and Experimental Pediatrics
• /
• v.51 no.9
• /
• pp.964-970
• /
• 2008

Purpose : Methylmalonic aciduria (MMA) and propionic aciduria (PA) are inborn errors in the catabolism of branched-chain amino acids. The study was undertaken to investigate the genotypes and clinical features of Korean patients with MMA and PA. Methods : This study examined 12 patients with MMA and eight with PA. We analyzed various clinical features, laboratory findings, treatments, and neuro-developmental outcomes. Diagnoses were based on the presence of characteristic compounds detected by amino acid analysis in serum and organic acid analysis in urine. Mutation analysis was performed in the genes of MUT, MMAA, MMAB, and MMACHC for MMA and PCCA and PCCB for PA. Results : Among the 20 patients, six patients were diagnosed before one month of age and nine patients were diagnosed after the newborn period. Five patients were diagnosed via a neonatal screening test. Patients with early-onset forms had more severe illness at presentation and generally poor outcomes. A favorable outcome was obtained in 55% patients; most of them were of a late-onset type or diagnosed by neonatal mass screening test without symptoms. Genotypes were confirmed in all patients with MMA. We detected 11 different mutations by MUT gene analysis in 10 patients, and three different mutations in MMACHC genes in two patients. PCCA and PCCB gene mutations were identified in 14 of the 16 alleles, in eight patients with PA. Conclusion : Organic aciduria is a fatal disease; however, better outcomes are expected whenever early diagnosis and prompt management are made possible. Mutation analysis is useful for confirming diagnoses and planning management strategies.

• Journal of Genetic Medicine
• /
• v.7 no.1
• /
• pp.59-66
• /
• 2010

Purpose: Quantitative fluorescent polymerase chain reaction (QF-PCR) allows for the rapid prenatal diagnosis of common aneuploidies. The main advantages of this assay are its low cost, speed, and automation, allowing for large-scale application. However, despite these advantages, it is not a routine method for prenatal aneuploidy screening in Korea. Our objective in the present study was to validate the performance of QF-PCR using short tandem repeat (STR) markers in a Korean population as a means for rapid prenatal diagnosis. Material and Methods: A QF-PCR assay using an Elucigene kit (Gen-Probe, Abingdon, UK), containing 20 STR markers located on chromosomes 13, 18, 21, X and Y, was performed on 847 amniotic fluid (AF) samples for prenatal aneuploidy screening referred for prenatal aneuploidy screening from 2007 to 2009. The results were then compared to those obtained using conventional cytogenetic analysis. To evaluate the informativity of STR markers, the heterozygosity index of each marker was determined in all the samples. Results: Three autosomes (13, 18, and 21) and X and Y chromosome aneuploidies were detected in 19 cases (2.2%, 19/847) after QF-PCR analysis of the 847 AF samples. Their results are identical to those of conventional cytogenetic analysis, with 100% positive predictive value. However, after cytogenetic analysis, 7 cases (0.8%, 7/847) were found to have 5 balanced and 2 unbalanced chromosomal abnormalities that were not detected by QF-PCR. The STR markers had a slightly low heterozygosity index (average: 0.76) compared to those reported in Caucasians (average: 0.80). Submicroscopic duplication of D13S634 marker, which might be a unique finding in Koreans, was detected in 1.4% (12/847) of the samples in the present study. Conclusion: A QF-PCR assay for prenatal aneuploidy screening was validated in our institution and proved to be efficient and reliable. However, we suggest that each laboratory must perform an independent validation test for each STR marker in order to develop interpretation guidelines of the results and must integrate QF-PCR into the routine cytogenetic laboratory workflow.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.16 no.3
• /
• pp.141-147
• /
• 2016

Hypophosphatasia is caused by the mutations in ALPL, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). It can be inherited either in an autosomal dominant or recessive manner. Clinically, hypophophosphatasia is characterized by skeletal findings similar to those in rickets or osteomalacia, but serum alkaline phosphatase levels are decreased in the affected patients. Hypophosphatasia can be classified into six clinical forms according to age at diagnosis and severity of symptoms: perinatal lethal, infantile, childhood, adult, odontohypophosphatasia, and perinatal benign. As being a very rare disease, only one case has been reported in Korean population. Here we describe a case with perinatal benign hypophosphatasia with recessive ALPL mutations. Bowing of lower legs was detected in prenatal period and low serum alkaline phosphatase level was noted after birth. During the follow-up evaluation for 4.5 years, bone mineralization and legs bowing were improved but the growth retardation was persistent. As the recombinant bone-targeted human TNSALP became available, the clinical improvement of the affected patients is expected including the case described here with this treatment. More efforts are needed to identify the cases affected by hypophosphatasia.

• Journal of Genetic Medicine
• /
• v.5 no.1
• /
• pp.47-54
• /
• 2008

Purpose : Fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells offers the opportunity for rapid screening of aneuploidies and has become an integral part of the current practice in many clinical cytogenetics laboratories. Here, we retrospectively analyzed the results of interphase FISH in 943 amniotic fluid samples and assessed the efficiency of FISH for rapid detection of aneuploidies. Methods : Interphase FISH for chromosome 13, 18, and 21 was performed in 943 consecutive amniotic fluid samples for rapid diagnosis of aneuploidies referred from 2004 to 2006. Karyotypes from standard cytogenetic analysis were compared to the FISH results. Results : A total of 45 chromosomal rearrangements (4.8%) were found after conventional cytogenetic analysis of the 943 amniotic fluid. After exclusion of known familiar chromosomal rearrangements and inversions (2.1%, 20/943), 2.7% (25/943) were found to have chromosomal abnormalities. Of this group, 0.7% (6/943) were chromosomal abnormalities not detectable by FISH and 2.0% (19/943) were numerical abnormalities detectable by FISH. All 14 cases of Down syndrome (Classic type, 13 cases; Robertsonian type, 1 case) and 5 cases of trisomy 18 were diagnosed and detected by FISH and there were no false-positive or -negative results (specificity and sensitivity=100%). Conclusion : The present study demonstrates that FISH can provide a rapid and sensitive clinical method for prenatal identification of chromosome aneuploidies. However, careful genetic counseling is essential to explain the limitations of FISH, including the inability to detect all chromosomal abnormalities and the possibilities of uninformative or false-negative results in some cases.

• Clinical and Experimental Pediatrics
• /
• v.50 no.9
• /
• pp.868-874
• /
• 2007

Purpose : We performed this study to investigate the perinatal and developmental features of the patients with congenital myotonic dystrophy (CDM) confirmed by the molecular genetic method and the clinical characteristics of their mother, and to identify the relation between the number of CTG repeats and the clinical severity.Methods : A retrospective review of the medical records and the results of the dystrophia myotonica protein kinase (DMPK) gene test was done for the patients who were confirmed as CDM through gene analysis from January 2001 to September 2006. Results : All of the eight patients (male 2, female 6) showed moderate to severe degree of perinatal distress and feeding difficulty associated with profound hypotonia. Three patients had the history of polyhydramnios and two patients had equinovarus deformity. The developmental milestones were delayed in all patients, which improved gradually with age. All of their mothers demonstrated myotonic symptoms and typical myopathic face. The number of CTG repeats in DMPK gene analysis ranged 1,000-2,083, and there was no significant correlation between the number of CTG repeats and the time of walking alone. Conclusion : All patients with CDM presented with severe hypotonia in perinatal period, and developmental delay thereafter, which were improved with age. All of their mothers manifested myotonic symptoms with typical myopathic face, and the identification of such features greatly contributed to the diagnosis of the patients. The number of CTG repeats had no significant influence on the motor development.