• Clinical and Experimental Pediatrics
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• v.59 no.1
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• pp.40-42
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• 2016

Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome who have a compound heterozygous or homozygous MMR gene mutation. We report a case of CRC in a 13-year-old patient with Lynch syndrome and congenital heart disease. This patient had a heterozygous mutation in MLH1 (an MMR gene), but no compound MMR gene defects, and a K-RAS somatic mutation in the cancer cells.

• Clinical and Experimental Pediatrics
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• v.60 no.3
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• pp.94-97
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• 2017

Trimethylaminuria (TMAuria), known as "fish odor syndrome," is a congenital metabolic disorder characterized by an odor resembling that of rotting fish. This odor is caused by the secretion of trimethylamine (TMA) in the breath, sweat, and body secretions and the excretion of TMA along with urine. TMAuria is an autosomal recessive disorder caused by mutations in flavin-containing monooxygenase 3 (FMO3). Most TMAuria cases are caused by missense mutations, but nonsense mutations have also been reported in these cases. Here, we describe the identification of a novel FMO3 gene mutation in a patient with TMAuria and her family. A 3-year-old girl presented with a strong corporal odor after ingesting fish. Genomic DNA sequence analysis revealed that she had compound heterozygous FMO3 mutations; One mutation was the missense mutation p.Val158Ile in exon 3, and the other was a novel nonsense mutation, p.Ser364X, in exon 7 of the FMO3 gene. Familial genetic analyses showed that the p.Val158Ile mutation was derived from the same allele in the father, and the p.Ser364X mutation was derived from the mother. This is the first description of the p.Ser364X mutation, and the first report of a Korean patient with TMAuria caused by novel compound heterozygous mutations.

• Journal of Genetic Medicine
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• v.16 no.1
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• pp.27-30
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• 2019

Smith-Kingsmore syndrome (SKS; OMIM 616638), also known as macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (MINDS; ORPHA 457485), is a rare autosomal dominant disorder, the prevalence of which is not known. It is caused by a heterozygous germline mutation in MTOR (OMIM 601231). Ten different MTOR germline mutations in 27 individuals have been reported in the medical literature to date. These were all gain-of-function missense variants, and about half of the 27 individuals had c.5395G>A p.(Glu1799Lys) in MTOR. Here, I report for the first time a Korean patient with the heterozygous germline mutation c.5395G>A p.(Glu1799Lys) in MTOR. It was found to be a de novo mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing. The patient showed typical clinical features of SKS, including macrocephaly/megalencephaly; moderate intellectual disability; seizures; behavioral problems; and facial dysmorphic features of curly hair, frontal bossing, midface hypoplasia, and hypertelorism.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.2
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• pp.58-62
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• 2022

Pompe disease (PD) is an autosomal recessive genetic disorder caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA). It is easy to hastily diagnose as patients if they have two pathogenic variants. Clinical pathologists misdiagnosed our infant and her mother as PD. Here, we report a case of pseudodeficiency in a potential late-onset Pompe disease (LOPD) carrier with a double dual variant, each in cis formation in a 3-month infant. The person who has two pathogenic variants was diagnosed as a carrier, not a patient. It was first reported in Korea. The patient had: two likely pathogenic heterozygous mutations on exon #4: c.752C>T (p.Ser251Leu), c.761C>T (p.Ser254Leu), and a heterozygous mutation on exon #12: c.1726G>A (p.Gly576Ser), also with a heterozygous mutation on exon #15: c.2065G>A (p.Glu689Lys). By presenting this case we emphasize the possibility of cis formation of genes which may cause pseudodeficiency, and potential LOPD carrier form. Hereby we suggest that thorough evaluation of GAA gene is essential among whom initially diagnosed as PD.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4319-4322
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• 2016

Background: FLT3 is mutated in about 1/3 of acute myelogenous leukemia (AML) patients. The aim of the present study was to report the prevalence of FLT3 mutations and comparison with prognostic factors in AML patients in the Northeastern of Iran. Materials and Methods: This cross-sectional study concerned 100 AML cases diagnosed based on bone marrow aspiration and peripheral blood. DNA for every AML patient was extracted and underwent PCR with FLT3-ITD primers. Results: The mean age at diagnosis was 28.5 years (range, 1-66 years), 52 patients (52%) being male. Out of 100 AML patients, 21 (21%) had FLT3 mutation, (17 with FLT3-ITD, 81%, and 4 with FLT3-D825, 19%). Of the 21, 14 (66.7%) had heterozygous mutation. There was no significant difference between age, sex and organomegaly between patients with FLT3 mutation versus FLT3 wild-type. Conclusions: Our frequency of FLT3 is in line with earlier fidnings of approximately 20 to 30% and also the prevalence of FLT3-ITD is more than FLT3-D35 mutation. There was no significant difference between prognostic factors (age and sex) in the patients with FLT3 mutation versus FLT3 wild-type. The prevalence of FLT3 heterozygous mutations is more that homozygous mutations in AML patients.

• Journal of Genetic Medicine
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• v.15 no.1
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• pp.24-27
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• 2018

Cornelia de Lange syndrome (CdLS) is a rare, clinically and genetically heterogeneous, multi-system developmental disorder caused by mutations in genes that encode components of the cohesin complex. X-linked CdLS caused by an SMC1A mutation is an extremely rare disease characterized by phenotypes milder than those of classic CdLS. In the Republic of Korea, based on a literature review, one family with SMC1A-related CdLS with mild phenotypes has been genetically confirmed to date. In this study, we describe the clinical features of a Korean boy with a hemizygous novel missense mutation and his mother with a heterozygous mutation, i.e., c.2447G>A (p.Arg816His) in SMC1A, identified by multi-gene panel sequencing. The proband had a mild phenotype with typical facial features and his mother exhibited a mild, subclinical phenotype. This study expands the clinical spectrum of patients with X-linked CdLS caused by SMC1A variants. Moreover, these findings reinforce the notion that a dominant negative effect in a carrier female with a heterozygous mutation in SMC1A results in a phenotype milder than that in a male patient with the same mutation.

• Childhood Kidney Diseases
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• v.23 no.2
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• pp.111-115
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• 2019

Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in CYP27B1. Clinical findings are growth retardation, hypotonia, muscle weakness, hypocalcemic seizures, and radiological features of rickets. We aimed to present the VDDR1A case with a genetic study of CYP27B1. The 14-month-old boy was admitted to the hospital due to a seizure. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), 25(OH) vitamin D, and 1,25(OH)2 vitamin D values were 5.1 mg/dL, 3.7 mg/dL, 705 IU/L, 429 pg/mL, 24.9 ng/mL, and 8.8 pg/mL, respectively. Radiological study showed cupping and fraying of the distal ulna and radius. The molecular genetic study revealed that the patient had a compound heterozygous mutation, $Phe443Profs^*24$ and c.589+1G>A, in CYP27B1. Genetic analysis of the family members presented that the mother was heterozygous for the mutation c.589+1G>A, and that the father was heterozygous for $Phe443Profs^*24$. The patient was treated with calcium lactate and calcitriol. Until now, six Korean patients with VDDR1A have been studied. Including this case, Korean patients with VDDR1A were found to have only three different mutations in 14 alleles, indicating that the mutation in the CYP27B1 gene is homogeneous in the Korean population.

• Childhood Kidney Diseases
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• v.27 no.2
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• pp.127-132
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• 2023

Cystinuria, a genetically inherited disorder, is a rare cause of kidney stones. It is characterized by impaired transport of cystine and amino acids in the proximal renal tubule and the small intestine. Most patients develop cystine stones throughout their lifetime. Recurrent renal stones need to be extracted by repeated urologic interventions. Treatment options of cystinuria for preventing stone recurrence are limited and poorly tolerated. In this study, we report a pediatric case of cystinuria with a heterozygous SLC3A1 mutation diagnosed by stone analysis, measurement of urine cystine excretion, and genetic analysis. There were recurrent renal stones despite repetitive shock wave lithotripsy and retrograde intrarenal surgery. However, the rate of stone formation seemed to be slower after D-penicillamine was added into adequate hydration and urinary alkalinization.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6803-6806
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• 2013

Background: Interferon regulatory factor 6 (IRF6) is a transcription factor with distinct and conserved DNA and protein binding domains. Mutations within the protein binding domain have been significantly observed in subjects with orofacial cleft relative to healthy controls. In addition, recent studies have identified loss of expression of IRF6 due to promoter hypermethylation in cutaneous squamous cell carcinomas. Since mutational events occurring within the conserved domains are likely to affect the function of a protein, we investigated whether regions within the IRF6 gene that encodes for the conserved protein binding domain carried mutations in oral squamous cell carcinoma (OSCC). Materials and Methods: Total chromosomal DNA extracted from 32 post surgical OSCC tissue samples were amplified using intronic primers flanking the exon 7 of IRF6 gene, which encodes for the major region of protein binding domain. The PCR amplicons from all the samples were subsequently resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: Sequencing analysis resulted in the identification of a mutation within exon 7 of IRF6 that occurred in heterozygous condition in 9% (3/32) of OSCC samples. The wild type codon TTC at position 252 coding for phenylalanine was found to be mutated to TAC that coded for tyrosine (F252Y). Conclusions: The present study identified for the first time a novel mutation within the conserved protein binding domain of IRF6 gene in tissue samples of subjects with OSCC.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.3
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• pp.157-162
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• 2003

Our earlier studies found a significant correlation between the activities of ranitidine N-oxidation catalyzed by hepatic flavin-containing monooxygenase (FMO) and the presence of mutations in exon 4 (E158K) and exon 7 (E308G) of the FMO3 gene in Korean volunteers. However, caffeine N-1 demethylation (which is also partially catalyzed by FMO) was not significantly correlated with these FMO3 mutations. In this study, we examined another common mutation (V257M) in exon 6 of FMO3 gene. The V257M variant, which is caused by a point mutation (G769A), was commonly observed (13.21% allele frequency) in our subjects (n=159). This point mutation causes a substitution of $Val^{257}$ to $Met^{257}$, with transformation of the secondary structure. The presence of this mutant allele correlated significantly with a reduction in caffeine N-1-demethylating activity, but was not correlated with the activity of N-oxidation of ranitidine. In a family study, the low FMO activity observed in a person heterozygous for a nonsense mutation in exon 4 (G148X) and heterozygous for missense mutation in exon 6 (V257M) of FMO3 was attributed to the mutations. Our results suggest that various point mutations in the coding regions of FMO3 may influence FMO3 activity according to the probe substrates of varying chemical structure that correlate with each mutation on the FMO3 gene.