• Clinical and Experimental Pediatrics
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• v.58 no.8
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• pp.309-312
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• 2015

Permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life. It is a rare disorder affecting one in 0.2-0.5 million live births. Mutations in the gene KCNJ11, encoding the subunit Kir6.2, and ABCC8, encoding SUR1 of the ATP-sensitive potassium ($K_{ATP}$) channel, are the most common causes of permanent neonatal diabetes mellitus. Sulfonylureas close the $K_{ATP}$ channel and increase insulin secretion. KCNJ11 and ABCC8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits. The mutation type, the presence of neurological features, and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy. More than 30 mutations in the KCNJ11 gene have been identified. Here, we present our experience with a patient carrying a novel p.H186D heterozygous mutation in the KCNJ11 gene who was successfully treated with oral sulfonylurea.

• Journal of Genetic Medicine
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• v.10 no.1
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• pp.1-6
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• 2013

Chronic granulomatous disease (CGD) is a rare inherited disorder of a defective NADPH oxidase enzyme, resulting in very low or no production of superoxide and subsequent reactive oxygen species. Consequently, patients with CGD are highly susceptible to severe bacterial and fungal infections. CGD is a genetically heterogeneous disease caused by defects in any one of the genes encoding the NADPH oxidase components. CGD generally affects about 3-4 per 1,000,000 individuals; thus, it is surprising that the prevalence of CGD on Jeju Island is 34.3 per 1,000,000 individuals. At present, 20 patients with CGD from 14 unrelated families on Jeju Island have been identified; nine males and 11 females. All patients with CGD tested on Jeju Island had an identical and homozygous mutation (c.7C>T in CYBA, p.Q3X in $p22^{phox}$). Therefore, all patients were autosomal recessive form of CGD. This strongly suggests that the unique and identical mutation in CYBA may be inherited from a common proband. Using mutation-specific primers to detect the mutated allele in CYBA, the frequency of subjects carrying a mutated allele was 1.3% of enrolled subjects from Seogwipo City. Further studies are necessary to elucidate how frequently this mutant allele occurs in the population on Jeju Island. Additionally, it is important to construct a national registry system to understand the pathophysiology of CGD and develop a strategy for long-term therapy.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.235-238
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• 2010

Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a mutation in the gene encoding the ${\alpha}-galactosidase$ A (GLA) enzyme. We report two cases of Fabry disease in a 12-year-old boy who had acroparesthesia and in his elder brother with milder symptoms who were diagnosed by GLA activity assays and the presence of the GLA gene mutation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.1
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• pp.71-75
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• 2016

Esophageal candidiasis is commonly seen in immunocompromised patients; however, candida esophagitis induced stricture is a very rare complication. We report the first case of esophageal stricture secondary to candidiasis in a glycogen storage disease (GSD) 1b child. The patient was diagnosed with GSD type 1b by liver biopsy. No mutation was found in the G6PC gene, but SLC37A4 gene sequencing revealed a compound heterozygous mutation (p.R28H and p.W107X, which was a novel mutation). The patient's absolute neutrophil count was continuously under $1,000/{\mu}L$ when he was over 6 years of age. He was admitted frequently for recurrent fever and infection, and frequently received intravenous antibiotics, antifungal agents. He complained of persistent dysphagia beginning at age 7 years. Esophageal stricture and multiple whitish patches were observed by endoscopy and endoscopic biopsy revealed numerous fungal hyphae consistent with candida esophagitis. He received esophageal balloon dilatation four times, and his symptoms improved.

• Journal of Interdisciplinary Genomics
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• v.4 no.1
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• pp.15-18
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• 2022

Hemophilia A is a rare X-linked congenital deficiency of clotting factor VIII (FVIII) that is traditionally diagnosed by measuring FVIII activity. Various mutations of the FVIII gene have been reported and they influence on the FVIII protein structure. A deficiency of or reduction in FVIII protein manifests as spontaneous or induced bleeding depending on the disease severity. Mutations of the FVIII gene provide important information on the severity of disease and inhibitor development. FVIII mutations also affect the discrepant activities found using different FVIII assays. FVIII activity is affected differently depending on the mutation site. Long-range PCR is commonly used to detect intron 22 inversion, the most common mutation in severe hemophilia. However, point mutations are also common in patients with hemophilia, and direct Sanger sequencing and copy number variant analysis are being used to screen for full mutations in the FVIII gene. Advances in molecular genetic methods, such as next-generation sequencing, may enable accurate analysis of mutations in the factor VIII gene, which may be useful in the diagnosis of mild to moderate hemophilia. Genetic analysis is also useful in diagnosing carriers and managing bleeding control. This review discusses the current knowledge about mutations in hemophilia and focuses on the clinical aspects associated with these mutations and the importance of genetic analysis.

• Journal of Genetic Medicine
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• v.18 no.2
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• pp.147-151
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• 2021

The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) (Online Mendelian Inheritance in Man #603736) is a rare autosomal dominant disorder and clinically features blepharophimosis with ptosis, a mask-like facial appearance, cryptorchidism, congenital heart defect, long thumbs/great toes, and thyroid dysfunction. The etiology of SBBYSS has been shown to be due to heterozygous KAT6B gene mutation. Here we report a case of a neonate with SBBYSS identified a novel mutation in KAT6B gene. The patient showed typical dysmorphic facies, cryptorchidism with micropenis, overriding fingers, and long thumbs and toes at birth. He had also hypothyroidism, large atrial septal defect, and sensorineural hearing loss. The next generation sequencing identified a heterozygous novel variant, c.5206C>T (p.Gln1736Ter) in KAT6B gene. At the 9 months of age, he underwent patch closure for atrial septal defect. Until the 12-month follow-up, he was under-developed.

• Childhood Kidney Diseases
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• v.26 no.2
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• pp.107-110
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• 2022

Nephrogenic diabetes insipidus, decreased ability to concentrate urine, with production of large amounts of urine, is caused by the refractory response of renal tubules to the action of antidiuretic hormone. This rare disorder, known as X-linked nephrogenic diabetes insipidus, is caused by a mutation in the AVPR2 gene. Because it is hereditary, most patients are male. This report highlights a case of nephrogenic diabetes insipidus in a 3-year 5-month-old female; upon presentation to the hospital, her symptoms included frequent urinationand consumptionof a significant amount ofwater,which had begun2 years ago. The results of blood tests showed increased levels of serum antidiuretic hormone, and sellar magnetic resonance imaging showed no abnormality. The results of the water restriction test and the desmopressin administration test confirmed the diagnosis of nephrogenic diabetes insipidus showing a partial response to desmopressin. The results of genetic testing indicated the presence of an AVPR2 mutation, a heterozygous missense mutation (p.Val88Met), suggesting inheritance of X-linked nephrogenic diabetes insipidus. This report describes a significant case of symptomaticX-linked nephrogenic diabetes insipidus in a female patient who showed a partial response to desmopressin.

• Genomics & Informatics
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• v.1 no.2
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• pp.75-79
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• 2003

Every protein can be characterized by either a distinct motif or a combination of motifs. Nevertheless, little is known about the relationships among (more than two) the motifs. Some of the proteins in the world are share motifs for evolutional or other biological benefits - they can save energy, time and resource for controlling and managing a variety of proteins. In some cases of motifs, the tendency is quite common and they can act the 'hub' motif of a network of the motif associations. The hubs are structurally and functionally important in themselves and also important in disease-related mutations. They will be highly resistant mutation to conserve their functions. But, in case of the a rare mutation, mutations on the position of hub can more easily cause fatal diseases.

• Journal of Genetic Medicine
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• v.10 no.1
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• pp.7-12
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• 2013

Familial Juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal dominant disorder, characterized by early onset of hyperuricemia, gout and progressive kidney disease. Hyperuricemia prior to renal impairment and decreased fractional excretion of uric acid are hallmarks of FJHN. Renal dysfunction gradually appears early in life and results in end-stage renal disease usually between the ages of 20 and 70 years. FJHN is mostly caused by mutations in the uromodulin gene located at 16p12. The course of FJHN is highly variable. Treatment includes management for hyperuricemia, gout and progressive kidney disease. Individuals with gout have been usually treated with allopurinol. But controversy exists as to whether uric acid lowering therapy prevents the progression of chronic kidney disease.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.1-4
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• 2016

Congenital aniridia is a rare ocular malformation that presents with severe hypoplasia of the iris and various ocular manifestations. Most cases of congenital aniridia are known to be related to mutations in the paired box gene-6 (PAX6 ), which is an essential gene in eye development. Herein, we report a familial case of autosomal dominant congenital aniridia with four affected members in 3 consecutive generations and describe the detailed ophthalmologic findings for one of these members. As expected, mutational analysis revealed a nonsense mutation (p.Ser122*) in the PAX6 gene. Thus, our findings reiterate the importance of PAX6 mutations in congenital aniridia.