• Childhood Kidney Diseases
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• v.25 no.2
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• pp.128-132
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• 2021

Morning glory syndrome (MGS) is a rare congenital optic disc anomaly with a characteristic fundal finding with severe visual impairment. It may occur in association with various systemic manifestations, even though most of the reported cases were isolated. A 6-year-old male visited the nephrology clinic with a history of microscopic hematuria and at the age of 12 years, he was diagnosed thin glomerular basement membrane nephropathy by kidney biopsy. After the following years, the patient had progressive deterioration of visual acuity, and diagnosed as MGS. Whole Exome Sequencing of this patient and his mother revealed heterozygous COL4A4 mutations [c.81_86del (p.Ile29_Leu30del)]. It is more reasonable to consider MGS seen in this patient as a coincidental finding of autosomal dominant Alport syndrome. To our knowledge, this case represents the first case report of autosomal dominant Alport syndrome associated with MGS.

• Genomics & Informatics
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• v.19 no.1
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• pp.2.1-2.10
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• 2021

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

• Korean Journal of Agricultural Science
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• v.49 no.3
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• pp.595-606
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• 2022

Industrial pig breeding has used the Duroc breed and terminal sires in a three-way crossbred system in Korea. This study identified the gene variation patterns related to carcass quality in crossbred pigs ([Landrace × Yorkshire] × Duroc) using whole-exome sequencing (WES). This study used crossbred pigs and divided them into two groups (first plus grade, n = 5; second grade, n = 5). Genomic DNA samples extracted from the loin muscles of both groups were submitted for WES. A set of validated single-nucleotide polymorphisms (SNPs: n = 102) were also subjected to the Kompetitive allele-specific polymerase chain reaction (KASP) to confirm the WES results in the loin muscles. Based on the WES, SNPs associated with meat quality were found on chromosomes 5, 10, and 15. We identified variations in three of the candidate genes, including kinesin family member 5B (KIF5B), GLI family zinc finger 2 (GLI2), and KIF26B, that were associated with meat color, marbling score, and backfat thickness. These genes were associated with meat quality and the mitogen-activated protein kinase (MAPK) and Hedgehog (Hh) signaling pathways in the crossbred pigs. These results may help clarify the mechanisms underlying high-quality meat in pigs.

• Journal of the Korean neurological association
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• v.30 no.4
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• pp.333-336
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• 2012

Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene is known to be associated with different clinical phenotypes; Silver syndrome, Charcot-Marie-Tooth type 2 with a dominant hand involvement and distal hereditary motor neuropathy type V (dHMN-V). Up to now, only two heterozygous mutations (N88S and S90L) in BSCL2 have been reported. We identified a N88S BSCL2 mutation in a dHMN-V family with a spastic gait by whole-exome sequencing. To our knowledge, this is the first report of a N88S BSCL2 mutation in Korean patient.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.1-7
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• 2023

Inherited metabolic disorders (IMD) are a group of disorders involving various metabolic pathways. Genetic diagnosis of IMD has been challenging because of extremely heterogeneous nature and extensive laboratory and/or phenotype overlap. Conventional genetic diagnosis was a gene-by-gene approach that needs a priori information on the causative genes that might underlie the IMD. Recent implementation of next-generation sequencing (NGS) technologies has changed the process of genetic diagnosis from a gene-by-gene approach to simultaneous analysis of targeted genes possibly associated with the IMD using gene panels or using whole exome/genome sequencing (WES/WGS) covering entire human genes. Clinical NGS tests can be a cost-effective approach for the rapid diagnosis of IMD with genetic heterogeneity and are becoming standard diagnostic procedures.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.2
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• pp.62-67
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• 2018

Hunter syndrome, also known as mucopolysaccharidosis Type II (MPS II), is one of the lysosomal storage diseases caused by a lack of the enzyme iduronate 2-sulfatase (I2S). Lack of the I2S enzyme activity leads to accumulation of the glycosaminoglycans (GAG), causing dysfunction of multiple organs and systems. MPS II is an X-linked recessive disease due to mutation of IDS gene located on long arm of the X chromosome (Xq28). To date, more than 350 mutations of IDS gene have been identified in Hunter syndrome. Phenotypes of MPS II are classified as either severe or attenuated depending on the degree of cognitive impairment. Because the phenotype of MPS II is related to the type of mutation, identifying mutations is useful in predicting prognosis. We recently had a case of MPS II diagnosed by exome sequencing in a 7 month old boy with infantile spasm uncontrolled by AED. He was diagnosed with hearing loss at 2 months of age, and he took vigabatrin and prednisolone to control infantile spasms diagnosed at 3 months of age. At 6 months of age, whole exome sequencing was performed to evaluate the infantile spasm and hearing loss in this patient, and the mutation c.851C>T (p.Pro284Leu) inherited from hemizygous mother was revealed. The results of urine Cetylpyridinium Chloride (CPC) precipitation test, which were negative until 8 months of age, were positive from 9 months of age. We report a case of MPS II diagnosed by exome sequencing and treated through enzyme replacement therapy from 9 months after birth.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.69-76
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• 2017

Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene on chromosome 7q21.3, and a type of urea cycle disorder that causes hyperammonemia. Although neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, a type of citrin deficiency, have been described well in many articles for several decades, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), the other type of citrin deficiency, has been only identified recently. There was previously no case report about FTTDCD in Korea. Patients with FTTDCD could present with loss of appetite, fatigue, failure to thrive, hypoglycemia, hypercitrullinemia, dyslipidemia, and an increased lactate/pyruvate ratio. Routine evaluation may not reveal the cause of hypoglycemia caused by citrin deficiency. We recently had a case that presented with recurrent hypoglycemia in a 30-month-old boy. Chemistry profiling, urine organic acid analysis, plasma acylcarnitine analysis, and hormone studies indicated values within the normal range or non-specific findings. Mutation analysis to identify the cause of hypoglycemia identified the subject as a compound heterozygote carrying each of the c.852_855del ($p.Met285Profs^*2$), and c.1177+1G>A mutant alleles. We report here on this unusual case of citrin deficiency presenting with FTTDCD for the first time in Korea.

• Journal of Life Science
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• v.24 no.3
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• pp.311-317
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• 2014

Distal myopathy with rimmed vacuoles (DMRV) or hereditary inclusion body myopathy 2 is an autosomal recessive muscular disorder characterized by early adult-onset weakness of distal muscles and rimmed vacuoles in muscle biopsy. Mutations in the UDP-N-acetylglucosamine 2-epimerase/N-ace-tylmannosamine kinase (GNE) gene are associated with the development of DMRV. In this study, whole exome sequencing (WES) revealed compound heterozygous GNE mutations of p.Asp176Val and p.Val572Leu in a patient with distal limb weakness. Three hundred healthy controls did not show these mutations. All other variants found in distal myopathy-relevant genes were polymorphic. These findings confirmed that the patient had DMRV. This work underscores the usefulness of WES in improving the molecular diagnosis of myopathy.

• Clinical and Experimental Pediatrics
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• v.61 no.12
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• pp.403-406
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• 2018

Floating-Harbor syndrome is a rare autosomal dominant genetic disorder associated with SRCAP mutation. To date, approximately 50 cases of Floating-Harbor syndrome have been reported, but none have been reported in Korea yet. Floating-Harbor syndrome is characterized by delayed bony maturation, unique facial features, and language impairment. Here, we present a 6-year-old boy with a triangular face, deep-set protruding eyes, low-set ears, wide nose with narrow nasal bridge, short philtrum, long thin lips, clinodactyly, and developmental delay that was transferred to our pediatric clinic for genetic evaluation. He showed progressive delay in the area of language and cognition-adaption as he grew. He had previously undergone chromosomal analysis at another hospital due to his language delay, but his karyotype was normal. We performed targeted exome sequencing, considering several syndromes with similar phenotypes. Library preparation was performed with the TruSight One sequencing panel, which enriches the sample for about 4,800 genes of clinical relevance. Massively parallel sequencing was conducted with NextSeq. An identified variant was confirmed by Sanger sequencing of the patient and his parents. Finally, the patient was confirmed as the first Korean case of Floating-Harbor syndrome with a novel SRCAP (Snf2 related CREBBP activator protein) mutation (c.7732dupT, p.Ser2578Phefs*6), resulting in early termination of the protein; it was not found in either of his healthy parents or a control population. To our knowledge, this is the first study to describe a boy with Floating-Harbor syndrome with a novel SRCAP mutation diagnosed by targeted exome sequencing in Korea.

• Journal of Genetic Medicine
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• v.13 no.1
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• pp.20-25
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• 2016

Purpose: Xeroderma pigmentosum (XP) is rare autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet light is deficient. We reported the first molecularly confirmed Korean patient of XP by targeted exome sequencing. The prevalence of XP included all subtype and carrier frequency of XP-A the using public data were estimated for the first time in South Korea. Materials and Methods: We described a 4-year-old Korean girl with clinical diagnosis of XP. We performed targeted exome sequencing in the patient for genetic confirmation considering disease genetic heterogeneity and for differential diagnosis. We verified a carrier frequency of c.390-1G>C in XPA gene known as mutational hot spot using Korean Reference Genome Data Base. We estimated the period prevalence of all subtypes of XP based on claims data of the Health Insurance Review and Assessment Service in South Korea. Results: We identified homozygous splicing mutation of XPA (c.390-1G>C) in the patient. The carrier frequency of risk for XPA (c.390-1G>C) was relatively high 1.608 e-03 (allele count 2/1244). The prevalence of XP in South Korea was 0.3 per million people. Conclusion: We expect that c.390-1G>C is hot spot for the mutation of XPA and possible founder variant in South Korea. However, the prevalence in South Korea was extremely low compared with Western countries and Japan.