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1.
Annals of Pediatric Endocrinology & Metabolism ; : 67-72, 2023.
Article in English | WPRIM | ID: wpr-966272

ABSTRACT

Coffin-Lowry syndrome (CLS, OMIM # 303600) is a rare X-linked disorder caused by mutations in RPS6KA3. CLS is characterized by facial dysmorphism, digit abnormalities, developmental delays, growth retardation, and progressive skeletal changes in male patients. Females with CLS are variably affected, complicating diagnosis. Here, we describe the clinical and molecular findings in a female Korean child with CLS and review the associated literature. A 5-year-old girl presented with short stature and developmental delays. She had a coarse facial appearance characterized by a prominent forehead, hypertelorism, thick lips, and hypodontia. She also had puffy tapering fingers and pectus excavatum. We performed exome sequencing and identified a novel, likely pathogenic, heterozygous variant, c.326_338delinsCTCGAGAC (p.Val109Alafs*10), in RPS6KA3 (NM_004586.2). This is the first Korean female genetically diagnosed with CLS. In contrast to the delayed bone age reported in previous studies, our patient showed advanced bone age and central precocious puberty. CLS should be considered as a differential diagnosis of short stature, tapering fingers, and developmental delay. We suggest that molecular techniques can be a useful tool for diagnosis of rare disorders such as CLS because such conditions are not simple, and the associated spectrum of phenotypes can vary.

2.
Journal of Genetic Medicine ; : 22-26, 2022.
Article in English | WPRIM | ID: wpr-937948

ABSTRACT

Cerebrotendinous xanthomatosis (CTX) is a rare genetic disease caused by a deficiency of enzymes for the synthesis of bile acid, resulting in the accumulation of cholestanol with reduced chenodeoxycholic acid (CDCA) production and causing various symptoms such as chronic diarrhea in infancy, juvenile cataracts in childhood, tendon xanthomas in adolescence and young adulthood, and progressive neurologic dysfunction in adulthood. Because oral CDCA replacement therapy can effectively prevent disease progression, early diagnosis and treatment are critical in CTX. This study reports the case of CTX in a 10-year-old male who presented with Achilles tendon xanthoma and mild intellectual disability. Biochemical testing showed normal cholesterol and sitosterol levels but elevated cholestanol levels. Genetic testing showed compound heterozygous variants of CYP27A1, c.379C>T (p.Arg127Trp), and c.1214G>A (p.Arg405Gln), which confirmed the diagnosis of CTX. The patient had neither cataracts nor other focal neurologic deficits and showed no abnormalities on brain imaging. The patient received oral CDCA replacement therapy without any adverse effects; thereafter, the cholestanol level decreased and no disease progression was noted. The diagnostic possibility of CTX should be considered in patients with tendon xanthoma and normolipidemic conditions to prevent neurological deterioration.

3.
Pediatric Gastroenterology, Hepatology & Nutrition ; : 1-6, 2021.
Article in English | WPRIM | ID: wpr-903086

ABSTRACT

Next-generation sequencing (NGS) technologies have changed the process of genetic diagnosis from a gene-by-gene approach to syndrome-based diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS). A priori information on the causative genes that might underlie a genetic condition is a prerequisite for genetic diagnosis before conducting clinical NGS tests. Theoretically, DPS, DES, and DGS do not require any information on specific candidate genes. Therefore, clinical NGS tests sometimes detect disease-related pathogenic variants in genes underlying different conditions from the initial diagnosis. These clinical NGS tests are expensive, but they can be a cost-effective approach for the rapid diagnosis of rare disorders with genetic heterogeneity, such as the glycogen storage disease, familial intrahepatic cholestasis, lysosomal storage disease, and primary immunodeficiency. In addition, DES or DGS may find novel genes that that were previously not linked to human diseases.

4.
Pediatric Gastroenterology, Hepatology & Nutrition ; : 1-6, 2021.
Article in English | WPRIM | ID: wpr-895382

ABSTRACT

Next-generation sequencing (NGS) technologies have changed the process of genetic diagnosis from a gene-by-gene approach to syndrome-based diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS). A priori information on the causative genes that might underlie a genetic condition is a prerequisite for genetic diagnosis before conducting clinical NGS tests. Theoretically, DPS, DES, and DGS do not require any information on specific candidate genes. Therefore, clinical NGS tests sometimes detect disease-related pathogenic variants in genes underlying different conditions from the initial diagnosis. These clinical NGS tests are expensive, but they can be a cost-effective approach for the rapid diagnosis of rare disorders with genetic heterogeneity, such as the glycogen storage disease, familial intrahepatic cholestasis, lysosomal storage disease, and primary immunodeficiency. In addition, DES or DGS may find novel genes that that were previously not linked to human diseases.

5.
Yonsei Medical Journal ; : 224-230, 2021.
Article in English | WPRIM | ID: wpr-875615

ABSTRACT

Purpose@#Nontuberculous mycobacteria (NTM) is ubiquitous in the environment, but NTM lung disease (NTM-LD) is uncommon. Since exposure to NTM is inevitable, patients who develop NTM-LD are likely to have specific susceptibility factors, such as primary ciliary dyskinesia (PCD). PCD is a genetically heterogeneous disorder of motile cilia and is characterized by chronic respiratory tract infection, organ laterality defect, and infertility. In this study, we performed whole exome sequencing (WES) and investigated the genetic characteristics of adult NTM patients with suspected PCD. @*Materials and Methods@#WES was performed in 13 NTM-LD patients who were suspected of having PCD by clinical symptoms and/or ultrastructural ciliary defect observed by transmission electron microscopy. A total of 45 PCD-causing genes, 23 PCDcandidate genes, and 990 ciliome genes were analyzed. @*Results@#Four patients were found to have biallelic loss-of-function (LoF) variants in the following PCD-causing genes: CCDC114, DNAH5, HYDIN, and NME5. In four other patients, only one LoF variant was identified, while the remaining five patients did not have any LoF variants. @*Conclusion@#At least 30.8% of NTM-LD patients who were suspected of having PCD had biallelic LoF variants, and an additional 30.8% of patients had one LoF variant. Therefore, PCD should be considered in patients with NTM-LD with symptoms or signs suspicious of PCD.

6.
Annals of Laboratory Medicine ; : 326-330, 2020.
Article in English | WPRIM | ID: wpr-811096

ABSTRACT

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by progressive proximal muscle weakness and atrophy. Given the recent introduction of gene therapies, knowledge of the SMA carrier frequency in various populations has become important for developing screening programs for this disease. In total, 1,581 anonymous DNA samples from an umbilical cord blood bank were tested for SMN1 and SMN2 gene copies using a multiplex ligation-dependent probe amplification assay. Twenty-nine of the 1,581 newborns [1.83%; 95% confidence interval (CI), 1.25–2.66%] were SMA carriers with one copy of SMN1, and no homozygous SMN1 deletion was detected. The carrier frequency in this population was estimated to be 1,834 per 100,000 (95% CI, 1,254–2,659) or 1 in 55 (95% CI, 1/79–1/38). Our data indicate that SMA carriers are not uncommon in the Korean population and may serve as a reference for designing a population screening program in Korea.

7.
Allergy, Asthma & Immunology Research ; : 292-305, 2020.
Article in English | WPRIM | ID: wpr-785340

ABSTRACT

PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.


Subject(s)
Humans , Agammaglobulinemia , Diagnosis , Exome , Flow Cytometry , Genetic Testing , Granulomatous Disease, Chronic , Immunophenotyping , Korea , Leukocytes , Lymphocyte Subsets , Lymphohistiocytosis, Hemophagocytic , Phenotype , Retrospective Studies , Seoul , Severe Combined Immunodeficiency , Tertiary Healthcare
8.
Annals of Laboratory Medicine ; : 99-100, 2020.
Article in English | WPRIM | ID: wpr-762478

ABSTRACT

No abstract available.


Subject(s)
Breast Neoplasms , Breast , Genetic Testing
9.
Annals of Laboratory Medicine ; : 606-606, 2019.
Article in English | WPRIM | ID: wpr-762426

ABSTRACT

This erratum is being published to revise the website address of the Korean Reference Genome Database (KRGDB) and correct two typographical errors in the article.

10.
Allergy, Asthma & Respiratory Disease ; : 158-164, 2019.
Article in Korean | WPRIM | ID: wpr-762189

ABSTRACT

Filamin A is an actin-binding protein and, in humans, is encoded by FLNA gene in the long arm of X chromosome. Filamin A plays a role in the formation of cytoskeleton by crosslinking actin filaments in cytoplasm. FLNA mutations affect cytoskeletal regulatory processes and cellular migrating abnormalities that result in periventricular heterotopia. A 5-month-old girl was hospitalized because of breathing difficulty and was diagnosed as having periventricular heterotopia with laryngomalacia, cricopharyngeal incoordination, pulmonary hypertension, and chronic lung disease. A genetic test was performed to find the cause of periventricular heterotopia, and FLNA gene mutation (c.5998+1G>A) was confirmed for the first time in Korea. After discharge, she developed respiratory failure due to a viral infection at 8 months of her age. In spite of management with mechanical ventilation, she died of pneumothorax and pulmonary hemorrhage. Herein, we report a case of FLNA gene mutation who presented with periventricular nodular heterotopia with respiratory insufficiency.


Subject(s)
Female , Humans , Infant , Actin Cytoskeleton , Arm , Ataxia , Cytoplasm , Cytoskeleton , Filamins , Hemorrhage , Hypertension, Pulmonary , Korea , Laryngomalacia , Lung Diseases , Periventricular Nodular Heterotopia , Pneumothorax , Respiration , Respiration, Artificial , Respiratory Insufficiency , X Chromosome
11.
Tuberculosis and Respiratory Diseases ; : 88-89, 2019.
Article in English | WPRIM | ID: wpr-719612

ABSTRACT

No abstract available.


Subject(s)
Nontuberculous Mycobacteria
13.
Laboratory Medicine Online ; : 166-170, 2019.
Article in English | WPRIM | ID: wpr-760499

ABSTRACT

Mycobacterium shimoidei is a nontuberculous mycobacterium (NTM), and is rarely reported as a pathogen causing the NTM pulmonary disease. We describe here the case of a 52-year-old male with symptoms such as chronic cough and a history of pulmonary tuberculosis. Radiologic studies revealed a cavitary lesion in the left upper lobe of his lung. Sputum culture was positive for NTM, which was later identified as M. shimoidei using 16S rRNA and hsp65 sequencing. The patient's symptoms, radiologic evidence, and positive culture results together substantiate that this is the first case of M. shimoidei pulmonary disease from Korea.


Subject(s)
Humans , Male , Middle Aged , Cough , Korea , Lung , Lung Diseases , Mycobacterium , Nontuberculous Mycobacteria , Sputum , Tuberculosis, Pulmonary
14.
Laboratory Medicine Online ; : 94-98, 2019.
Article in English | WPRIM | ID: wpr-760484

ABSTRACT

Actinotignum schaalii is an emerging uropathogen; however, routine culture protocols and usual phenotypic methods do not allow for easy detection and identification. Herein, we report the first Korean case of urinary tract infection caused by A. schaalii in a 79-year-old patient with prostate cancer. A gram-positive rod bacterium was isolated from the patient's urine after 2 days of culture and identified as A. schaalii using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and DNA target sequencing.


Subject(s)
Aged , Humans , DNA , Mass Spectrometry , Prostatic Neoplasms , Urinary Tract Infections , Urinary Tract
15.
Korean Journal of Pediatrics ; : 193-197, 2019.
Article in English | WPRIM | ID: wpr-760199

ABSTRACT

Alport syndrome (ATS) is an inherited glomerular disease caused by mutations in one of the type IV collagen novel chains (α3, α4, and α5). ATS is characterized by persistent microscopic hematuria that starts during infancy, eventually leading to either progressive nephritis or end-stage renal disease. There are 3 known genetic forms of ATS, namely X-linked ATS, autosomal recessive ATS, and autosomal dominant ATS. About 80% of patients with ATS have X-linked ATS, which is caused by mutations in the type IV collagen α5 chain gene, COL4A5. Although an 80% mutation detection rate is observed in men with X-linked ATS, some difficulties do exist in the genetic diagnosis of ATS. Most mutations are point mutations without hotspots in the COL4A3, COL4A4, and COL4A5 genes. Further, there are insufficient data on the detection of COL4A3 and COL4A4 mutations for their comparison between patients with autosomal recessive or dominant ATS. Therefore, diagnosis of ATS in female patients with no apparent family history can be challenging. Therefore, in this study, we used whole-exome sequencing (WES) to identify mutations in type IV collagen in 2 girls with glomerular basement membrane structural changes suspected to be associated with ATS; these patients had no relevant family history. Our results revealed de novo c.4688G>A (p.Arg1563Gln) and c.2714G>A (p.Gly905Asp) mutations in COL4A5. Therefore, we suggest that WES is an effective approach to obtain genetic information in ATS, particularly in female patients without a relevant family history, to detect unexpected DNA variations.


Subject(s)
Child , Female , Humans , Male , Collagen Type IV , Diagnosis , DNA , Exome , Glomerular Basement Membrane , Hematuria , Kidney Failure, Chronic , Korea , Nephritis , Nephritis, Hereditary , Point Mutation
16.
Journal of the Korean Ophthalmological Society ; : 380-386, 2019.
Article in Korean | WPRIM | ID: wpr-738617

ABSTRACT

PURPOSE: To discuss the clinical course and diagnosis of corneal dysplasia in a xeroderma pigmentosum patient based on a genetic evaluation. CASE SUMMARY: A 42-year-old female visited our clinic for decreased left visual acuity and corneal opacity. She had undergone several surgeries previously due to the presence of basosquamous carcinoma in the left lower eyelid, neurofibroma, and malignant melanoma of the facial skin. The patient showed repeated corneal surface problems, with a suspicious dendritic lesion; however, antiviral therapy was ineffective, and herpes simplex virus polymerase chain reaction results were negative. Despite regular follow-ups, the patient showed neovascularization around the corneal limbus and an irregular corneal surface. We performed corneal debridement with autologous serum eye drops for treatment. The patient's visual acuity and corneal surface improved after the procedure. The impression cytology result was corneal dysplasia. In whole exome sequencing, two pathogenic variants and one likely pathogenic variant of the POLH gene were detected. CONCLUSIONS: This is the first genetically identified xeroderma pigmentosum case with ophthalmological lesions of the eyelid and cornea in Korea. Debridement of the irregular corneal surface and autologous serum eye drop administration in xeroderma pigmentosum could be helpful for improving visual acuity.


Subject(s)
Adult , Female , Humans , Carcinoma, Basosquamous , Cornea , Corneal Opacity , Debridement , Diagnosis , Exome , Eyelids , Follow-Up Studies , Ichthyosis , Korea , Limbus Corneae , Melanoma , Neurofibroma , Ophthalmic Solutions , Polymerase Chain Reaction , Simplexvirus , Skin , Visual Acuity , Xeroderma Pigmentosum
17.
Yonsei Medical Journal ; : 798-800, 2018.
Article in English | WPRIM | ID: wpr-716422

ABSTRACT

Unverricht-Lundborg disease (ULD) is a form of progressive myoclonus epilepsy characterized by stimulation-induced myoclonus and seizures. This disease is an autosomal recessive disorder, and the gene CSTB, which encodes cystatin B, a cysteine protease inhibitor, is the only gene known to be associated with ULD. Although the prevalence of ULD is higher in the Baltic region of Europe and the Mediterranean, sporadic cases have occasionally been diagnosed worldwide. The patient described in the current report showed only abnormally enlarged restriction fragments of 62 dodecamer repeats, confirming ULD, that were transmitted from both her father and mother who carried the abnormally enlarged restriction fragment as heterozygotes with normal-sized fragments. We report the first case of a genetically confirmed patient with ULD in Korea.


Subject(s)
Humans , Blotting, Southern , Cystatin B , Cysteine Proteases , Diagnosis , Europe , Fathers , Heterozygote , Korea , Mothers , Myoclonic Epilepsies, Progressive , Myoclonus , Prevalence , Seizures , Unverricht-Lundborg Syndrome
18.
Journal of Clinical Neurology ; : 374-380, 2018.
Article in English | WPRIM | ID: wpr-715685

ABSTRACT

BACKGROUND AND PURPOSE: The etiologies and frequencies of cerebellar ataxias vary between countries. Our primary aim was to determine the frequency of each diagnostic group of cerebellar ataxia patients in a Korean population. METHODS: We reviewed the medical records of patients who were being followed up between November 1994 and February 2016. We divided patients with cerebellar ataxias into familial and non-familial groups and analyzed the frequency of each etiology. Finally, we categorized patients into genetic, sporadic, secondary, and suspected genetic, but undetermined ataxia. RESULTS: A total of 820 patients were included in the study, among whom 136 (16.6%) familial patients and 684 (83.4%) non-familial cases were identified. Genetic diagnoses confirmed 98/136 (72%) familial and 72/684 (11%) nonfamilial patients. The overall etiologies of progressive ataxias comprised 170 (20.7%) genetic, 516 (62.9%) sporadic, 43 (5.2%) secondary, and 91 (11.1%) undetermined ataxia. The most common cause of ataxia was multiple-system atrophy (57.3%). In the genetic group, the most common etiology was spinocerebellar ataxia (152/170, 89.4%) and the most common subtype was spinocerebellar ataxia-3.38 of 136 familial and 53 of 684 sporadic cases (91/820, 11.1%) were undetermined ataxia. CONCLUSIONS: This is the largest epidemiological study to analyze the frequencies of various cerebellar ataxias in a Korean population based on the large database of a tertiary hospital movement-disorders clinic in South Korea. These data would be helpful for clinicians in constructing diagnostic strategies and counseling for patients with cerebellar ataxias.


Subject(s)
Humans , Ataxia , Atrophy , Cerebellar Ataxia , Counseling , Diagnosis , Epidemiologic Studies , Friedreich Ataxia , Korea , Medical Records , Spinocerebellar Ataxias , Tertiary Care Centers
19.
Experimental Neurobiology ; : 550-563, 2018.
Article in English | WPRIM | ID: wpr-719049

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is frequently linked to microtubule abnormalities and mitochondrial trafficking defects. Whole exome sequencing (WES) of patient-parent trios has proven to be an efficient strategy for identifying rare de novo genetic variants responsible for sporadic ALS (sALS). Using a trio-WES approach, we identified a de novo RAPGEF2 variant (c.4069G>A, p.E1357K) in a patient with early-onset sALS. To assess the pathogenic effects of this variant, we have used patient-derived skin fibroblasts and motor neuron-specific overexpression of the RAPGEF2-E1357K mutant protein in Drosophila. Patient fibroblasts display reduced microtubule stability and defective microtubule network morphology. The intracellular distribution, ultrastructure, and function of mitochondria are also impaired in patient cells. Overexpression of the RAPGEF2 mutant in Drosophila motor neurons reduces the stability of axonal microtubules and disrupts the distribution of mitochondria to distal axons and neuromuscular junction (NMJ) synapses. We also show that the recruitment of the pro-apoptotic protein BCL2-associated X (BAX) to mitochondria is significantly increased in patient fibroblasts compared with control cells. Finally, increasing microtubule stability through pharmacological inhibition of histone deacetylase 6 (HDAC6) rescues defects in the intracellular distribution of mitochondria and BAX. Overall, our data suggest that the RAPGEF2 variant identified in this study can drive ALS-related pathogenic effects through microtubule dysregulation.


Subject(s)
Humans , Amyotrophic Lateral Sclerosis , Axons , Drosophila , Exome , Fibroblasts , Histone Deacetylases , Microtubules , Mitochondria , Motor Neurons , Mutant Proteins , Mutation, Missense , Neurodegenerative Diseases , Neuromuscular Junction , Skin , Synapses
20.
Annals of Laboratory Medicine ; : 283-286, 2018.
Article in English | WPRIM | ID: wpr-714423

ABSTRACT

No abstract available.

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