• Journal of Genetic Medicine
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• v.13 no.1
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• pp.51-54
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• 2016

Centronuclear myopathy (CNM) is a rare congenital myopathy that is pathologically characterized by the centrally located nuclei in most of the muscle fibers. On clinical examination, dynamin 2 (DNM2)-related CNM typically shows distal dominant muscle atrophy, ptosis, ophthalmoplegia, and contracture. The reported cases of CNM in Caucasian studies show a high prevalence rate of early-onset ptosis and ophthalmoplegia and correlated with the severity of the disease. However, Asian reports show a low prevalence and late-onset ocular symptoms in DNM2-related CNM patients. p.R465W is one of the most commonly found mutations in Western countries, and all the cases showed ocular symptoms. The proband and his daughter had no ocular symptoms despite harboring the same p.R465W mutation. This family makes us speculate that ocular symptoms in DNM2-related CNM are influenced by ethnic background. In addition, this is the first familial case of DNM2-related CNM in Korea.

• The Journal of the Korean bone and joint tumor society
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• v.20 no.2
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• pp.99-103
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• 2014

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder characterised by a variety of different tumor types in children and young adults. That contains with a germline mutation in the tumor suppressor gene Tumor Protein p53 (TP53). That is extremely rare. Furthermore, this is sometimes overlooked. Here, we report a case of LFS which was confirmed by mutational analysis of the p53 gene. Also, literature review is intended to improve understanding of this disease entity.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.234-238
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• 2003

Fanconi syndrome is a generalized functional disorder of the proximal tubule of the kidney and is characterized by aminoaciduria, glycosuria, hyperphosphaturia, dehydration, rickets, and growth failure. Nephrocalcinosis and hypercalciuria are rare manifestations of Fanconi syndrome. There is no case report of Fanconi syndrome complicated with nephrocalcinosis and hypercalciuria in Korea. A 6-year-old boy presented with genu valgum and waddling gaits for about 3 years. There was no family history of renal disease and his physical examination was normal except for genu valgum and corrected cleft lip and palate. Laboratory investigations showed generalized aminoaciduria, glycosuria, hyperphosphaturia, hypercalciuria, and low-molecular weight proteinuria including ${\beta}$-microglobulin. Serum 25-OH vitamin $D_3$ was within the normal range, and $1,25-(OH)_2$ vitamin $D_3$ was elevated. Bilateral renal medullary hyperechogenicity was demonstrated by ultrasonography. Analysis of the CLCN5 gene revealed no mutation. Here we describe a boy with Fanconi syndrome complicated with nophrocalcinosis and discuss the differential diagnosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.6
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• pp.601-607
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• 2019

Pancreaticopleural fistula (PPF) a fistulous connection between the pancreas and pleural space due to prolonged chronic pancreatitis (CP). PPF is a very rare complication which presents in 0.4% of chronic pancreatitis cases, especially among children. We report a case involving a 3-year-old boy who presented with pleural effusion caused by a PPF, a complication of hereditary pancreatitis, which was, for the first time in Korea, successfully managed with endoscopic treatment. Chest radiography and computed tomography showed massive pleural effusion. Percutaneous catheter drainage was performed. High amylase levels were observed in the pleural fluid and serum, suggesting PPF. The patient was managed with bowel rest and octreotide infusion. Endoscopic retrograde cholangiopancreatography revealed CP, and pleural effusion was successfully managed with stent placement. PRSS1 genetic screening revealed R122H mutation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.2
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• pp.201-206
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• 2019

Benign recurrent intrahepatic cholestasis (BRIC), a rare cause of cholestasis, is characterized by recurrent episodes of cholestasis without permanent liver damage. BRIC type 2 (BRIC2) is an autosomal recessive disorder caused by ABCB11 mutations. A 6-year-old girl had recurrent episodes of jaundice. At two months of age, jaundice and hepatosplenomegaly developed. Liver function tests showed cholestatic hepatitis. A liver biopsy revealed diffuse giant cell transformation, bile duct paucity, intracytoplasmic cholestasis, and periportal fibrosis. An ABCB11 gene study revealed novel compound heterozygous mutations, including c.2075+3A>G in IVS17 and p.R1221K. Liver function test results were normal at 12 months of age. At six years of age, steatorrhea, jaundice, and pruritus developed. Liver function tests improved following administration of phenylbutyrate and rifampicin. Her younger brother developed jaundice at two months of age and his genetic tests revealed the same mutations as his sister. This is the first report of BRIC2 confirmed by ABCB11 mutations in Korean siblings.

• Clinical and Experimental Pediatrics
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• v.63 no.12
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• pp.469-476
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• 2020

The major pathogens that cause atypical pneumonia are Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. Community-acquired pneumonia (CAP) caused by M. pneumoniae or C. pneumoniae is common in children and presents as a relatively mild and self-limiting disease. CAP due to L. pneumophila is very rare in children and progresses rapidly, with fatal outcomes if not treated early. M. pneumoniae, C. pneumoniae, and L. pneumophila have no cell walls; therefore, they do not respond to β-lactam antibiotics. Accordingly, macrolides, tetracyclines, and fluoroquinolones are the treatments of choice for atypical pneumonia. Macrolides are the first-line antibiotics used in children because of their low minimum inhibitory concentrations and high safety. The incidence of pneumonia caused by macrolide-resistant M. pneumoniae that harbors point mutations has been increasing since 2000, particularly in Korea, Japan, and China. The marked increase in macrolide-resistant M. pneumoniae pneumonia (MRMP) is partly attributed to the excessive use of macrolides. MRMP does not always lead to clinical nonresponsiveness to macrolides. Furthermore, severe complicated MRMP responds to corticosteroids without requiring a change in antibiotic. This implies that the hyper-inflammatory status of the host can induce clinically refractory pneumonia regardless of mutation. Empirical macrolide therapy in children with mild to moderate CAP, particularly during periods without M. pneumoniae epidemics, may not provide additional benefits over β-lactam monotherapy and can increase the risk of MRMP.

• Neonatal Medicine
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• v.28 no.1
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• pp.59-63
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• 2021

An important, albeit rare, cause of fetal bradycardia is long QT syndrome (LQTS). Congenital LQTS is an ion channelopathy caused by mutations in genes encoding cardiac ion channel proteins. Fetal onset of LQTS imposes high risk of life-threatening tachyarrhythmias and sudden cardiac death. Here, we report the case of a female newborn with fetal onset of bradycardia and a 2:1 atrioventricular (AV) block. After birth, a 12-lead electrocardiogram (ECG) revealed bradycardia with QT prolongation of a corrected QT (QTc) interval of 680 ms and pseudo 2:1 AV block. Genetic testing identified a heterozygous Gly402Ser (c.1204G>A) mutation in CACNA1C, confirming the diagnosis of LQTS type 8 (LQT8). The patient received propranolol at a daily dose of 2 mg/kg. Mexiletine was subsequently administered owing to the sustained prolongation of the QT interval and pseudo 2:1 AV block. One week after mexiletine inception, the ECG still showed QT interval prolongation (QTc, 632 ms), but no AV block was observed. There were no life-threatening tachyarrhythmias in a follow-up period of 13 months.

• Genomics & Informatics
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• v.20 no.3
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• pp.28.1-28.7
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• 2022

We described a clinical, laboratory, and genetic presentation of a pathogenic variant of the CYP1B1 gene through a report of a case of primary congenital glaucoma and a trio analysis of this candidate variant in the family with the Sanger sequencing method and eventually completed our study with the secondary/incidental findings. This study reports a rare case of primary congenital glaucoma, an 8-year-old female child with a negative family history of glaucoma and uncontrolled intraocular pressure. This case's whole-exome sequencing data analysis presents a homozygous pathogenic single nucleotide variant in the CYP1B1 gene (NM_000104:exon3:c.G1103A:p.R368H). At the same time, this pathogenic variant was obtained as a heterozygous state in her unaffected father but not her mother. The diagnosis was made based on molecular findings of whole-exome sequencing data analysis. Therefore, the clinical reports and bioinformatics findings supported the relation between the candidate pathogenic variant and the disease. However, it should not be forgotten that primary congenital glaucoma is not peculiar to the CYP1B1 gene. Since the chance of developing autosomal recessive disorders with low allele frequency and unrelated parents is extraordinary in offspring. However, further data analysis of whole-exome sequencing and Sanger sequencing method were applied to obtain the type of mutation and how it was carried to the offspring.

• Annals of dermatology
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• v.31 no.3
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• pp.325-330
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• 2019

Cowden's disease is a rare autosomal dominant, multiple hamartoma syndrome with characteristic mucocutaneous lesions. It is associated with abnormalities of the breast, thyroid, and gastrointestinal tract; and is characterized by multiple hamartomas in the gastrointestinal tract and mucocutaneous lesions such as trichilemmomas, oral papillomatosis, facial papules, and acral keratosis. A 21-year-old male patient presented with erythematous facial papules, oral mucosal papillomatosis, and punctate palmoplantar hyperkeratosis indicating a definite case of Cowden's disease. This disease derives from variable expression resulting from a mutation in the PTEN gene. Gastrointestinal endoscopy and colonoscopy revealed multiple hamartomas in the stomach and colon. On thyroid ultrasonography, several probable benign nodules were noted in the right thyroid gland. He had no pertinent family history and no other systemic findings. Further regular laboratory and image studies will be planned for our patient, as well as his family members. Sporadic Cowden's disease is rarely observed. Herein, we report a case of Cowden's disease without known family history. Dermatologists should be aware of the possibility of Cowden syndrome based on its several dermatologic findings.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.3
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• pp.99-106
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• 2018

Mucolipidosis type III (pseudo-Hurler polydystrophy) is a mucolipids degrading disorder caused by a mutation in the GNPTAB gene and is inherited by autosomal recessive. It is diagnosed by examining highly concentrated mucolipids in blood and the diagnosis can be confirmed by genetic testing. Mucolipidosis type III is a rare and progressive metabolic disorder. Its initial signs and symptoms usually occur around 3 years of age. Clinical manifestations of the disease include slow growth, joint stiffness, arthralgia, skeletal abnormalities, heart valve abnormalities, recurrent respiratory infection, distinctive facial features, and mild intellectual disability. Here, we are presenting two siblings of mucolipidosis type III, a 4-year-old female and a 2 years and 7 months old male with features of delayed growth and coarse face. The diagnosis was confirmed by [c.2715+1G>A(p.Glu906Leufs*4), c.2544del(p.Glu849Lysfs*22)] mutation in targeted gene panel sequencing. In this case, c.2544del is a heterozygote newly identified mutation in mucolipidosis type III and was not found in the control group including the genome aggregation database. And it is interpreted as a pathogenic variant considering the association with phenotype. Here, we report a Korean mucolipidosis type III patients with novel mutations in GNPTAB gene who have been treated since early childhood. Owing to recent development of molecular genetic techniques, it was possible to make early diagnosis and treatment with pamidronate was initiated appropriately in case 1. In addition to these supportive therapies, efforts must be made to develop fundamental treatment for patients with early diagnosis of mucolipidosis.