1.Identification of the PROM1 Mutation p.R373C in a Korean Patient With Autosomal Dominant Stargardt-like Macular Dystrophy.
Jong Min KIM ; Chung LEE ; Ga In LEE ; Nayoung K D KIM ; Chang Seok KI ; Woong Yang PARK ; Byoung Joon KIM ; Sang Jin KIM
Annals of Laboratory Medicine 2017;37(6):536-539
Stargardt-like macular dystrophy 4 (STGD4) is a rare macular dystrophy characterized by bull's eye atrophy of the macula and the underlying retinal pigment epithelium. Patients with STGD4 show decreased central vision, which often progresses to severe vision loss. The PROM1 gene encodes prominin-1, which is a 5-transmembrane glycoprotein also known as CD133 and is involved in photoreceptor disk morphogenesis. PROM1 mutations have been identified as genetic causes for STGD4 and other retinal degenerations such as retinitis pigmentosa. We report a case of STGD4 with a PROM1 p.R373C mutation in a Korean patient. Ophthalmic examinations of a 38-yr old man complaining of decreased visual acuity revealed bilateral atrophic macular lesions consistent with STGD4. Targeted exome sequencing of known inherited retinal degeneration genes revealed a heterozygous missense mutation c.1117C>T (p.R373C) of PROM1, which was confirmed by Sanger sequencing. To the best of our knowledge, this is the first case of a PROM1 mutation causing STGD4 in Koreans.
Atrophy
;
Exome
;
Glycoproteins
;
Humans
;
Macular Degeneration*
;
Morphogenesis
;
Mutation, Missense
;
Retinal Degeneration
;
Retinal Pigment Epithelium
;
Retinitis Pigmentosa
;
Visual Acuity
2.Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia.
Kunho BAE ; Ju Sun SONG ; Chung LEE ; Nayoung K D KIM ; Woong Yang PARK ; Byoung Joon KIM ; Chang Seok KI ; Sang Jin KIM
Annals of Laboratory Medicine 2017;37(5):438-442
Choroideremia is a rare X-linked disorder causing progressive chorioretinal atrophy. Affected patients develop night blindness with progressive peripheral vision loss and eventual blindness. Herein, we report two Korean families with choroideremia. Multimodal imaging studies showed that the probands had progressive loss of visual field with characteristic chorioretinal atrophy, while electroretinography demonstrated nearly extinguished cone and rod responses compatible with choroideremia. Sanger sequencing of all coding exons and flanking intronic regions of the CHM gene revealed a novel small deletion at a splice site (c.184_189+3delTACCAGGTA) in one patient and a deletion of the entire exon 9 in the other. This is the first report on a molecular genetic diagnosis of choroideremia in Korean individuals. Molecular diagnosis of choroideremia should be widely adopted for proper diagnosis and the development of new treatment modalities including gene therapy.
Atrophy
;
Blindness
;
Choroideremia*
;
Clinical Coding
;
Diagnosis
;
Electroretinography
;
Exons
;
Genetic Therapy
;
Humans
;
Introns
;
Molecular Biology
;
Multimodal Imaging
;
Night Blindness
;
Visual Fields
3.The Effect of Globus Pallidus Interna Deep Brain Stimulation on a Dystonia Patient with the GNAL Mutation Compared to Patients with DYT1 and DYT6
Jong Hyeon AHN ; Ah Reum KIM ; Nayoung K D KIM ; Woong Yang PARK ; Ji Sun KIM ; Minkyeong KIM ; Jongkyu PARK ; Jung Il LEE ; Jin Whan CHO ; Kyung Rae CHO ; Jinyoung YOUN
Journal of Movement Disorders 2019;12(2):120-124
OBJECTIVE: The aim of this study was to investigate the efficacy of globus pallidus interna deep brain stimulation (GPi-DBS) for treating dystonia due to the GNAL mutation. METHODS: We provide the first report of a dystonia patient with a genetically confirmed GNAL mutation in the Korean population and reviewed the literature on patients with the GNAL mutation who underwent GPi-DBS. We compared the effectiveness of DBS in patients with the GNAL mutation compared to that in patients with DYT1 and DYT6 in a previous study. RESULTS: Patients with the GNAL mutation and those with DYT1 had higher early responder rates (GNAL, 5/5, 100%; DYT1, 7/7, 100%) than did patients with DYT6 (p = 0.047). The responder rates at late follow-up did not differ statistically among the three groups (p = 0.278). The decrease in the dystonia motor scale score in the GNAL group was 46.9% at early follow-up and 63.4% at late follow-up. CONCLUSION: GPi-DBS would be an effective treatment option for dystonia patients with the GNAL mutation who are resistant to medication or botulinum toxin treatment.
Botulinum Toxins
;
Deep Brain Stimulation
;
Dystonia
;
Follow-Up Studies
;
Globus Pallidus
;
Humans
4.Good Laboratory Standards for Clinical Next-Generation Sequencing Cancer Panel Tests.
Jihun KIM ; Woong Yang PARK ; Nayoung K D KIM ; Se Jin JANG ; Sung Min CHUN ; Chang Ohk SUNG ; Jene CHOI ; Young Hyeh KO ; Yoon La CHOI ; Hyo Sup SHIM ; Jae Kyung WON
Journal of Pathology and Translational Medicine 2017;51(3):191-204
Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS. This consensus standard proposal consists of two parts: laboratory guidelines and requirements for clinical NGS laboratories. The laboratory guidelines part addressed several important issues across multistep NGS cancer panel tests including choice of gene panel and platform, sample handling, nucleic acid management, sample identity tracking, library preparation, sequencing, analysis and reporting. Requirements for clinical NGS tests were summarized in terms of documentation, validation, quality management, and other required written policies. Together with appropriate pathologist training and international laboratory standards, these laboratory standards would help molecular pathology laboratories to successfully implement NGS cancer panel tests in clinic. In this way, the oncology community would be able to help patients to benefit more from personalized cancer medicine.
Consensus
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High-Throughput Nucleotide Sequencing
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Humans
;
Korea
;
Pathology, Molecular
;
Practice Guidelines as Topic
;
Quality Control
5.Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas
Hyemi SHIN ; Jason K. SA ; Joon Seol BAE ; Harim KOO ; Seonwhee JIN ; Hee Jin CHO ; Seung Won CHOI ; Jong Min KYOUNG ; Ja Yeon KIM ; Yun Jee SEO ; Je-Gun JOUNG ; Nayoung K. D. KIM ; Dae-Soon SON ; Jongsuk CHUNG ; Taeseob LEE ; Doo-Sik KONG ; Jung Won CHOI ; Ho Jun SEOL ; Jung-Il LEE ; Yeon-Lim SUH ; Woong-Yang PARK ; Do-Hyun NAM
Cancer Research and Treatment 2020;52(1):41-50
Purpose:
Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas.
Materials and Methods:
To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization.
Results:
Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene.
Conclusion
We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.
6.Targeted exome sequencing resolves allelic and the genetic heterogeneity in the genetic diagnosis of nephronophthisis-related ciliopathy.
Hee Gyung KANG ; Hyun Kyung LEE ; Yo Han AHN ; Je Gun JOUNG ; Jaeyong NAM ; Nayoung K D KIM ; Jung Min KO ; Min Hyun CHO ; Jae Il SHIN ; Joon KIM ; Hye Won PARK ; Young Seo PARK ; Il Soo HA ; Woo Yeong CHUNG ; Dae Yeol LEE ; Su Young KIM ; Woong Yang PARK ; Hae Il CHEONG
Experimental & Molecular Medicine 2016;48(8):e251-
Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end-stage renal failure during childhood and adolescence and exhibits an autosomal recessive pattern of inheritance. Genetic diagnosis is quite limited owing to genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step-wise screening of Sanger sequencing and targeted exome sequencing for the genetic diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by Sanger sequencing in phenotypically classified patients. Known pathogenic mutations were identified in 12 patients (21.8%); homozygous deletions of NPHP1 in 4 juvenile nephronophthisis patients, IQCB1/NPHP5 mutations in 3 Senior–Løken syndrome patients, a CEP290/NPHP6 mutation in 1 Joubert syndrome patient, and TMEM67/MKS3 mutations in 4 Joubert syndrome patients with liver involvement. In the remaining undiagnosed patients, we applied targeted exome sequencing of 34 ciliopathy-related genes to detect known pathogenic mutations in 7 (16.3%) of 43 patients. Another 18 likely damaging heterozygous variants were identified in 13 NPHP-RC genes in 18 patients. In this study, we report a variety of pathogenic and candidate mutations identified in 55 patients with NPHP-RC in Korea using a step-wise application of two genetic tests. These results support the clinical utility of targeted exome sequencing to resolve the issue of allelic and genetic heterogeneity in NPHP-RC.
Adolescent
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Diagnosis*
;
Exome*
;
Genetic Heterogeneity*
;
Humans
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Kidney Failure, Chronic
;
Korea
;
Liver
;
Mass Screening
;
Wills