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1.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-785397

RESUMO

BACKGROUND: Pathogenic variants of USH1C, encoding a PDZ-domain-containing protein called harmonin, have been known to cause autosomal recessive syndromic or nonsyndromic hearing loss (NSHL). We identified a causative gene in a large Korean family with NSHL showing a typical pattern of autosomal dominant (AD) inheritance.METHODS: Exome sequencing was performed for five affected and three unaffected individuals in this family. Following identification of a candidate gene variant, segregation analysis and functional studies, including circular dichroism and biolayer interferometry experiments, were performed.RESULTS: A novel USH1C heterozygous missense variant (c.667G>T;p.Gly223Cys) was shown to segregate with the NSHL phenotype in this family. This variant affects an amino acid residue located in the highly conserved carboxylate-binding loop of the harmonin PDZ2 domain and is predicted to disturb the interaction with cadherin-related 23 (cdh23). The affinity of the variant PDZ2 domain for a biotinylated synthetic peptide containing the PDZ-binding motif of cdh23 was approximately 16-fold lower than that of the wild-type PDZ2 domain and that this inaccessibility of the binding site was caused by a conformational change in the variant PDZ2 domain.CONCLUSIONS: A heterozygous variant of USH1C that interferes with the interaction between cdh23 and harmonin causes novel AD-NSHL.


Assuntos
Sítios de Ligação , Dicroísmo Circular , Exoma , Perda Auditiva , Audição , Humanos , Interferometria , Fenótipo , Testamentos
2.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-785340

RESUMO

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.


Assuntos
Agamaglobulinemia , Diagnóstico , Exoma , Citometria de Fluxo , Testes Genéticos , Doença Granulomatosa Crônica , Humanos , Imunofenotipagem , Coreia (Geográfico) , Leucócitos , Subpopulações de Linfócitos , Linfo-Histiocitose Hemofagocítica , Fenótipo , Estudos Retrospectivos , Seul , Imunodeficiência Combinada Severa , Atenção Terciária à Saúde
3.
Cancer Research and Treatment ; : 1117-1127, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763168

RESUMO

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.


Assuntos
Animais , Carboplatina , Causas de Morte , Tratamento Farmacológico , Exoma , Feminino , Expressão Gênica , Genoma , Xenoenxertos , Humanos , Camundongos , Razão de Chances , Neoplasias Ovarianas , Ovário , Paclitaxel , Recidiva , Análise de Sequência de RNA , Estatística como Assunto
4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763121

RESUMO

PURPOSE: Half of the world's gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer. MATERIALS AND METHODS: We performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls. RESULTS: We showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer. CONCLUSION: Our result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.


Assuntos
Exoma , Extremo Oriente , Feminino , Variação Genética , Genoma , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Incidência , Desequilíbrio de Ligação , Mortalidade , Razão de Chances , Próstata , Células-Tronco , Neoplasias Gástricas
5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762621

RESUMO

Vanishing white matter (VWM) disease is an autosomal recessive disorder that affects the central nervous system of a patient, and is caused by the development of pathogenic mutations in any of the EIF2B1-5 genes. Any dysfunction of the EIF2B1-5 gene encoded eIF2B causes stress-provoked episodic rapid neurological deterioration in the patient, followed by a chronic progressive disease course. We present the case of a patient with an infantile-onset VWM with the pre-described specific clinical course, subsequent neurological aggravation induced by each viral infection, and the noted consequent progression into a comatose state. Although the initial brain magnetic resonance imaging did not reveal specific pathognomonic signs of VWM to distinguish it from other types of demyelinating leukodystrophy, the next-generation sequencing studies identified heterozygous missense variants in EIF2B3, including a novel variant in exon 7 (C706G), as well as a 0.008% frequency reported variant in exon 2 (T89C). Hence, the characteristic of unbiased genomic sequencing can clinically affect patient care and decisionmaking, especially in terms of the consideration of genetic disorders such as leukoencephalopathy in pediatric patients.


Assuntos
Encéfalo , Sistema Nervoso Central , Coma , Fator de Iniciação 2B em Eucariotos , Exoma , Éxons , Humanos , Leucoencefalopatias , Imagem por Ressonância Magnética , Assistência ao Paciente , Substância Branca
6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762611

RESUMO

Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates and infants with an incidence of one in 2,000 to one in 4,000 newborns. Primary CH can be caused by thyroid dysgenesis and thyroid dyshormonogenesis. CH due to a TG gene mutation is one cause of thyroid dyshormonogenesis and can be characterized by goitrous CH with absent or low levels of serum thyroglobulin (Tg). In the present case, a 15-day-old neonate was referred to us with elevated thyroid stimulating hormone detected during a neonatal screening test. At the age of 34 months, extensive genetic testing was performed, including targeted exome sequencing for hypothyroidism, and revealed compound heterozygous mutations in the TG gene. Sanger sequencing of both parents’ DNA samples revealed a c.3790T> C (p.Cys1264Arg) mutation located at exon 17 inherited from the mother, and a c.4057C> T (p.Gln1353*) mutation located at exon 19 was inherited from the father. The c.4057C> T (p.Gln1353*) mutation located at exon 19 has never been reported and, therefore, is a new discovery. We report a case of primary permanent CH with compound heterozygous mutations of the TG gene, including a novel mutation.


Assuntos
Hipotireoidismo Congênito , DNA , Exoma , Éxons , Pai , Testes Genéticos , Humanos , Hipotireoidismo , Incidência , Lactente , Recém-Nascido , Mães , Triagem Neonatal , Tireoglobulina , Disgenesia da Tireoide , Glândula Tireoide , Tireotropina
7.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762587

RESUMO

Idiopathic infantile hypercalcemia is characterized by hypercalcemia, dehydration, vomiting, and failure to thrive, and it is due to mutations in 24-hydroxylase (CYP24A1). Recently, mutations in sodium-phosphate cotransporter (SLC34A1) expressed in the kidney were discovered as an additional cause of idiopathic infantile hypercalcemia. This report describes a female infant admitted for evaluation of nephrocalcinosis. She presented with hypercalcemia, hypercalciuria, low intact parathyroid hormone level, and high 1,25-dihydroxyvitamin D3 level. Exome sequencing identified novel compound heterozygous mutations in SLC34A1 (c.1337G>A, c.1483C>T). The patient was treated with fluids for hydration, furosemide, a corticosteroid, and restriction of calcium/vitamin D intake. At the age of 7 months, the patient's calcium level was within the normal range, and hypercalciuria waxed and waned. Renal echogenicity improved on the follow-up ultrasonogram, and developmental delay was not noted. In cases of hypercalcemia with subsequent hypercalciuria, DNA analysis for SLC34A1 gene mutations and CYP24A1 gene mutations should be performed. Further studies are required to obtain long-term data on hypercalciuria and nephrocalcinosis.


Assuntos
Calcitriol , Cálcio , Desidratação , DNA , Exoma , Insuficiência de Crescimento , Feminino , Seguimentos , Furosemida , Humanos , Hipercalcemia , Hipercalciúria , Hipofosfatemia , Lactente , Rim , Nefrocalcinose , Hormônio Paratireóideo , Valores de Referência , Proteínas Cotransportadoras de Sódio-Fosfato , Ultrassonografia , Vitamina D , Vitamina D3 24-Hidroxilase , Vômito
8.
Neonatal Medicine ; : 240-245, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-786434

RESUMO

Baller-Gerold syndrome is a rare autosomal recessive disorder characterized by premature fusion of the cranial sutures and malformation of the upper limb extremities at birth. Although the pathogenesis of Baller-Gerold Syndrome is not fully understood, it is mainly caused by mutations in the RecQ like helicase 4 (RECQL4) gene located on chromosome 8q24.3, which encodes the RECQL4 protein involved in normal DNA replication and repair. This study reports the case of a female premature infant with craniosynostosis of bilateral coronal sutures, resulting in a dysmorphic face and hypoplastic thumbs on both hands at birth, which are consistent with the core characteristics of Baller-Gerold syndrome. Diagnostic whole exome sequencing of the patient revealed a homozygous deletion from exon 13 to 18 in the RECQL4 gene. To the best of my knowledge, this is the first reported case of Baller-Gerold syndrome with RECQL4 gene mutation confirmed by diagnostic whole exome sequencing in Korea.


Assuntos
Suturas Cranianas , Craniossinostoses , Replicação do DNA , Exoma , Éxons , Extremidades , Feminino , Mãos , Deformidades da Mão , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Coreia (Geográfico) , Parto , Suturas , Polegar , Extremidade Superior
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-775131

RESUMO

OBJECTIVE@#To explore the value and significance of the clinical application of whole exome sequencing (WES) in monogenic hereditary disorders in critically ill newborns.@*METHODS@#The critically ill newborns in the neonatal intensive care unit with suspected hereditary diseases or unclear clinical diagnosis from June 2016 to December 2018 were enrolled. The whole blood samples from both newborns and parents were collected for WES. The detected genetic mutations were classified, the mutations associated with clinical phenotypes were searched for, and Sanger sequencing was performed to verify the mutations.@*RESULTS@#A total of 45 newborns were enrolled, including 22 males and 23 females, and the median age of onset was 2.0 days. Of the 45 newborns, 12 (27%) were confirmed with monogenic hereditary disorders by molecular diagnostics, and the median age at diagnosis was 31.5 days. Of the 12 newborns with monogenic hereditary disorders, 5 (42%) were partially associated with clinical phenotypes but confirmed with monogenic hereditary disorders by additional information supplement and analysis. The improvement rate of newborns with monogenic hereditary disorders was 67% (8/12) after treatment.@*CONCLUSIONS@#WES technology is a powerful tool for finding genetic mutations in monogenic hereditary disorders in critically ill newborns and can play a crucial role in clinical decision-making. However, a comprehensive interpretation of sequence data requires physicians to take the clinical phenotypes and the results of WES into consideration simultaneously.


Assuntos
Estado Terminal , Exoma , Feminino , Humanos , Recém-Nascido , Masculino , Mutação , Fenótipo , Sequenciamento Completo do Exoma
10.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-766742

RESUMO

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), which is caused by mutations in SACS gene, is a very rare neurodegenerative disorder characterized by the clinical triad of early onset cerebellar ataxia, pyramidal tract features, and sensorimotor polyneuropathy. Herein, we report a 35-year-old Korean male who presented with gait disturbance and lower extremity weakness. Neuroimaging and ophthalmologic evaluation revealed features consistent with ARSACS. Mutation in SACS gene was demonstrated in clinical exome sequence analysis and the patient was finally diagnosed as ARSACS.


Assuntos
Adulto , Ataxia , Ataxia Cerebelar , Exoma , Marcha , Humanos , Extremidade Inferior , Masculino , Espasticidade Muscular , Doenças Neurodegenerativas , Neuroimagem , Polineuropatias , Tratos Piramidais , Análise de Sequência , Degenerações Espinocerebelares
11.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-760882

RESUMO

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive multisystemic disease that is associated with the liver, kidney, skin, and central nervous and musculoskeletal systems. ARC occurs as a result of mutations in the VPS33B (Vacuolar protein sorting 33 homolog B) or VIPAR (VPS33B interacting protein, apical-basolateral polarity regulator) genes. A female infant presented with neonatal cholestasis with a severe clinical outcome. She was diagnosed with ARC syndrome using targeted exome sequencing (TES). Exome sequencing revealed compound heterozygous mutations, c.707A>T and c.239+5G>A, in VPS33B, where c.707A>T was a novel variant; the resultant functional protein defects were predicted via in silico analysis. c.239+5G>A, a pathogenic mutation that affects splicing, is found in less than 0.1% of the general population. Invasive techniques, such as liver biopsies, did not contribute to a differential diagnosis of ARC syndrome; thus, early TES together with clinical presentations constituted an apparently accurate diagnostic procedure.


Assuntos
Biópsia , Colestase , Simulação por Computador , Diagnóstico Diferencial , Exoma , Feminino , Humanos , Lactente , Rim , Fígado , Sistema Musculoesquelético , Transporte Proteico , Pele
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765174

RESUMO

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive disorder caused by a defect in the immunoglobulin mu binding protein 2 (IGHMBP2) gene, leading to motor neuron degeneration. We identified an infant with SMARD1 by targeted exome sequencing from a consanguineous Syrian family having a history of recurrent infant deaths. The patient initially presented intrauterine growth retardation, poor sucking, failure to thrive, and respiratory failure at the age of two months, and an inborn error of metabolism was suspected at first. Over a period of one month, the infant showed rapid progression of distal muscular weakness with hand and foot contractures, which were suggestive of neuromuscular disease. Using targeted exome sequencing, the mutation in IGHMBP2 was confirmed, although the first report was normal. Targeted exome sequencing enabled identification of the genetic cause of recurrent mysterious deaths in the consanguineous family. Additionally, it is suggested that a detailed phenotypic description and communication between bioinformaticians and clinicians is important to reduce false negative results in exome sequencing.


Assuntos
Proteínas de Transporte , Contratura , Exoma , Insuficiência de Crescimento , Retardo do Crescimento Fetal , , Mãos , Humanos , Imunoglobulinas , Morte do Lactente , Lactente , Metabolismo , Neurônios Motores , Debilidade Muscular , Atrofia Muscular Espinal , Doenças Neuromusculares , Insuficiência Respiratória
13.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-764505

RESUMO

KBG syndrome is an autosomal dominant syndrome presenting with macrodontia, distinctive facial features, skeletal anomalies, and neurological problems caused by mutations in the ankyrin repeat domain 11 (ANKRD11) gene. The diagnosis of KBG is difficult in very young infants as the characteristic macrodontia and typical facial features are not obvious. The youngest patient diagnosed to date was almost one year of age. We here describe a 2-month-old Korean boy with distinctive craniofacial features but without any evidence of macrodontia due to his very early age. He also had a congenital megacolon without ganglion cells in the rectum. A de novo deletion of exons 5–9 of the ANKRD11 gene was identified in this patient by exome sequencing and real-time genomic polymerase chain reaction. As ANKRD11 is involved in the development of myenteric plexus, a bowel movement disorder including a congenital megacolon is not surprising in a patient with KBG syndrome and has possibly been overlooked in past cases.


Assuntos
Repetição de Anquirina , Diagnóstico , Exoma , Éxons , Cistos Glanglionares , Doença de Hirschsprung , Humanos , Lactente , Masculino , Transtornos dos Movimentos , Plexo Mientérico , Reação em Cadeia da Polimerase , Reto
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-719420

RESUMO

PURPOSE: Germline mutations within melanoma susceptibility genes are present only in minority of melanoma patients and it is expected that additional genes will be discovered with next generation sequence technology and whole-exome sequencing (WES). MATERIALS AND METHODS: Herein we performed WES on a cohort of 96 unrelated Polish patients with melanoma diagnosed under the age of 40 years who all screened negative for the presence of CDKN2A variants. A replication study using a set of 1,200 melanoma patient DNA samples and similarly large series of healthy controls was undertaken. RESULTS: We selected 21 potentially deleterious variants in 20 genes (VRK1, MYCT1, DNAH14, CASC3, MS4A12, PRC1, WWOX, CARD6, EXO5, CASC3, CASP8AP2, STK33, SAMD11, CNDP2, CPNE1, EFCAB6, CABLES1, LEKR1, NUDT17, and RRP15), which were identified by WES and confirmed by Sanger sequencing for an association study. Evaluation of the allele distribution among carriers and their relatives in available family trios revealed that these variants were unlikely to account for many familial cases of melanoma. Replication study revealed no statistically significant differences between cases and controls. CONCLUSION: Although most of the changes seemed to be neutral we could not exclude an association between variants in VRK1, CREB3L3, EXO5, and STK33 with melanoma risk.


Assuntos
Alelos , Estudos de Coortes , DNA , Exoma , Mutação da Fase de Leitura , Mutação em Linhagem Germinativa , Humanos , Incidência , Melanoma , Polônia
15.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-738617

RESUMO

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.


Assuntos
Adulto , Carcinoma Basoescamoso , Córnea , Opacidade da Córnea , Desbridamento , Diagnóstico , Exoma , Pálpebras , Feminino , Seguimentos , Humanos , Ictiose , Coreia (Geográfico) , Limbo da Córnea , Melanoma , Neurofibroma , Soluções Oftálmicas , Reação em Cadeia da Polimerase , Simplexvirus , Pele , Acuidade Visual , Xeroderma Pigmentoso
16.
Journal of Breast Cancer ; : 131-140, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-738409

RESUMO

When faced with a case of bilateral breast cancer (BBC), understanding how to differentiate bilateral primary breast cancer from contralateral metastatic breast cancer is essential for treatment, but clear identification criteria have not been established to date. Diverse events play different roles in the therapy and prognosis of BBC; hence, it is of great significance to detect a more comprehensive and convincing technique to make an accurate differential diagnosis. We report a rare case of synchronous BBC in a 61-year-old Chinese woman. Based on her clinical and pathological features and the use of whole exome sequencing and cancer genome analysis, we concluded that the patient developed contralateral metastatic breast cancer which metastasized from left to right. Therefore, together with clinical, pathological and cancer genomics information, we could precisely define the origin and evolution of BBC.


Assuntos
Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama , Mama , Diagnóstico , Diagnóstico Diferencial , Exoma , Feminino , Genoma , Genômica , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772014

RESUMO

OBJECTIVE@#To report on a case of 10p15.3 microdeletion syndrome and to explore its clinical and molecular characteristics.@*METHODS@#The patient was subjected to whole exome sequencing (WES), with his clinical features discussed in the light of literature review.@*RESULTS@#The patient presented with global developmental delay, hypotonia, autistic-like traits, mild facial dysmorphism and other features including short stature, small hands and feet, congenital heart disease and feeding difficulty. WES has detected deletions of ZMYND11, DIP2C, LARP4B, TUBB8, GTPBP4, IDI2, IDI1, WOR37 and ADARB2 genes on the short arm of chromosome 10. Among these, ZMYND11 gene been previously associated with intellectual disability.@*CONCLUSION@#The patient's phenotype was closely correlated with that of 10p15.3 microdeletion syndrome. Haploinsufficiency of the ZMYND11 gene may underlie the manifestations of 10p15.3 microdeletion syndrome.


Assuntos
Proteínas de Transporte , Deleção Cromossômica , Cromossomos Humanos Par 10 , Exoma , Proteínas de Ligação ao GTP , Humanos , Deficiência Intelectual , Proteínas Nucleares , Fenótipo , Tubulina (Proteína) , Sequenciamento Completo do Exoma
18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-760199

RESUMO

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.


Assuntos
Criança , Colágeno Tipo IV , Diagnóstico , DNA , Exoma , Feminino , Membrana Basal Glomerular , Hematúria , Humanos , Falência Renal Crônica , Coreia (Geográfico) , Masculino , Nefrite , Nefrite Hereditária , Mutação Puntual
19.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-766562

RESUMO

Over the last two decades, the systemic treatment of cancer has evolved from cytotoxic chemotherapy to targeted therapy and now immunotherapy. Next-generation sequencing (NGS) is entering clinical applications for cancer treatment through the help of more powerful computational analyses. The increasing number of targeted therapies approved by regulatory authorities (RAs) with or without biomarkers necessitates the screening of multiple biomarkers using NGS, which is now approved and reimbursed by Korean RAs for some types of malignancies. However, the clinical utility of NGS remains to be established as a prerequisite for its routine incorporation into clinical practice. Currently, the best scenario of NGS use in clinics is to enroll patients into clinical trials based on the detection of biomarkers, but this is only possible in the hospitals conducting the specific trial. The other scenario is the off-label use of a targeted drug, but this requires social consensus for future implementation. The clinical applications of NGS are expanding in terms of its platforms, from targeted sequencing to whole exome and RNA sequencing, and in terms of systemic therapy, from targeted therapy to immunotherapy. Research into tumor mutational burden and neoantigens is shedding new light on the clinical use of NGS in immunotherapy.


Assuntos
Biomarcadores , Consenso , Tratamento Farmacológico , Exoma , Humanos , Imunoterapia , Programas de Rastreamento , Uso Off-Label , Análise de Sequência de RNA
20.
Yonsei Medical Journal ; : 395-398, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-742542

RESUMO

Genitopatellar syndrome (GPS) is a rare disorder characterized by patellar hypoplasia, flexion contractures of the lower limbs, psychomotor retardation and genital and renal anomalies. We report the case of a female infant diagnosed with GPS to a KAT6B gene mutation, which was identified using whole exome sequencing.


Assuntos
Contratura , Exoma , Feminino , Humanos , Lactente , Coreia (Geográfico) , Extremidade Inferior
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