Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38.374
Filtrar
1.
Gene ; 764: 145105, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32882333

RESUMEN

Sarcoma (SARC) represents a group of highly histological and molecular heterogeneous rare malignant tumors with poor prognosis. There are few proposed classifiers for predicting patient's outcome. The Cancer Proteome Atlas (TPCA) and The Cancer Genome Atlas (TCGA) databases provide multi-omics datasets that enable a comprehensive investigation for this disease. The proteomic expression profile of SARC patients along with the clinical information was downloaded. 55 proteins were found to be associated with overall survival (OS) of patients using univariate Cox regression analysis. We developed a prognostic risk signature that comprises seven proteins (AMPKALPHA, CHK1, S6, ARID1A, RBM15, ACETYLATUBULINLYS40, and MSH6) with robust predictive performance using multivariate Cox stepwise regression analysis. Additionally, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters. Patients in high-risk group also have worse progression free intervals (PFI) than that of patients in low-risk group, but not for disease free intervals (DFI). The signature was validated using transcriptomic profile of SARC patients from TCGA. Potential mechanisms between high- and low-risk groups were identified using differentially expressed genes (DEGs) analysis. These DEGs were primarily enriched in RAS and MPAK signaling pathways. The signature protein molecules are candidate biomarkers for SARC, and the analysis of computational biology in tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinctly immune landscapes of high- and low-risk patients. Together, we constructed a prognostic signature for predicting outcomes for SARC integrating proteomic and transcriptomic profiles, this might have value in guiding clinical practice.


Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/inmunología , Pruebas Genéticas/métodos , Sarcoma/mortalidad , Microambiente Tumoral/inmunología , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/genética , Antígeno CTLA-4/inmunología , Conjuntos de Datos como Asunto , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunología , Supervivencia sin Progresión , Mapeo de Interacción de Proteínas , Proteómica , Curva ROC , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Sarcoma/inmunología , Transcriptoma/genética , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1205-1212, 2020 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-33179222

RESUMEN

With the rapid development and adaptation of high-throughput sequencing in clinical settings, application of exome sequencing (ES) has been gradually expanded from pediatric to prenatal diagnosis in recent years. There is an urgent need to establish criteria for clinical grade ES in order to facilitate such a complex testing. The standardization of pre- and post-test consultation, quality control for sample processing process and validation of bioinformatics data analysis, and more importantly data interpretation and reporting, as well as appropriate reporting scope, is of great importance for health care stakeholders. To achieve this, a committee composed of a wide range of healthcare professionals has proposed an ES standard for prenatal diagnosis. This has provided expert opinion on the genetic counseling and reporting standards of prenatal ES for the purpose of applying ES technology in prenatal setting.


Asunto(s)
Exoma , Diagnóstico Prenatal , Secuenciación del Exoma Completo , Consenso , Exoma/genética , Femenino , Asesoramiento Genético , Pruebas Genéticas , Humanos , Embarazo
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1217-1221, 2020 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-33179224

RESUMEN

OBJECTIVE: To explore strategies of prenatal genetic testing for fetuses featuring abnormal skeletal development. METHODS: Clinical data of 17 fetuses with skeletal dysplasia was collected. The results of genetic testing and outcome of pregnancy were analyzed. RESULTS: For 12 fetuses, the femur-to-foot length ratio was less than 0.9. Thirteen fetuses had a positive finding by genetic testing. One fetus was diagnosed with chromosomal aneuploidy, three were diagnosed with microdeletion/microduplications, and nine were diagnosed with hereditary bone diseases due to pathological variants of FGFR3, COL1A2, GPX4 or ALPL genes. CONCLUSION: For fetuses with skeletal dysplasia characterized by short femur, in addition to chromosomal karyotyping and microarray analysis, sequencing of FGFR3 and other bone disease-related genes can improve the diagnostic rate.


Asunto(s)
Enfermedades del Desarrollo Óseo/diagnóstico , Enfermedades del Desarrollo Óseo/genética , Diagnóstico Prenatal , Ultrasonografía Prenatal , Femenino , Feto/diagnóstico por imagen , Pruebas Genéticas , Humanos , Cariotipificación , Embarazo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1222-1225, 2020 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-33179225

RESUMEN

OBJECTIVE: To delineate the clinical feature and genetic basis of four patients with congenital neutropenia. METHODS: All patients were subjected to whole exome sequencing (WES). Suspected variants were verified by Sanger sequencing. RESULTS: The patients (two boys and two girls), aged 7 to 15 months, suffered from neutropenia and recurrent infections. Bone marrow smears showed a significant decrease in the proportion of rod-shaped and lobulated granulocytes, which suggested impaired development and maturation of bone marrow neutrophils. WES has discovered heterozygous variants (c.496G>A, c.58C>G, c.391G>A and IVS1+5T>A) of the ELANE gene in the patients. Among these, c.58C>G and IVS1+5T>A were unreported previously. Follow up revealed patients 1 and 3 had periodic neutropenia, while patients 2 and 4 had severe congenital neutropenia. After attaining the definite diagnosis, the patients were treated symptomatically. CONCLUSION: The main clinical feature of congenital neutropenia is refractory recurrent bacterial infections, for which mutations of the ELANE gene are a common cause. Two novel pathogenic ELANE variants have been discovered in this study.


Asunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea/diagnóstico , Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Neutropenia/congénito , Femenino , Pruebas Genéticas , Humanos , Lactante , Elastasa de Leucocito/genética , Masculino , Mutación , Neutropenia/diagnóstico , Neutropenia/genética
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1247-1249, 2020 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-33179231

RESUMEN

OBJECTIVE: To explore the genetic basis for a child with neonatal severe hyperparathyroidism. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Whole exome sequencing was carried out to screen potential mutations. Suspected mutation was verified by Sanger sequencing. RESULTS: The proband was found to carry compound heterozygous variants c.179G>A (p.Cys60Tyr) and c.1525G>A (p.Gly509Arg) of the CaSR gene. The c.179G>A variant was derived from her mother and was unreported previously. The c.1525G>A variant was derived from her father and known to be pathogenic. CONCLUSION: The compound heterozygous variants of c.179G>A and c.1525G>A of the CaSR gene probably underlie the disease in the patient. The results of genetic testing has enabled diagnosis and genetic counseling for her family.


Asunto(s)
Hiperparatiroidismo/diagnóstico , Hiperparatiroidismo/genética , Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/genética , Femenino , Asesoramiento Genético , Pruebas Genéticas , Humanos , Recién Nacido , Mutación , Linaje , Receptores Sensibles al Calcio/genética , Secuenciación del Exoma Completo
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1250-1252, 2020 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-33179232

RESUMEN

OBJECTIVE: To analyze the phenotype and genotype of a patient affected with inherited antithrombin deficiency. METHODS: All exons and exon-intron boundaries of the AT genes were subjected to PCR amplification and Sanger sequencing. The influence of variants on the disease was predicted using bioinformatic software (MutationTaster). RESULTS: The results of all coagulation tests were normal, though the antithrombin activity and antigen content of the proband and his father have decreased significantly (34%, 48% and 12.97 mg/dL, 15.60 mg/dL, respectively). His mother was normal. Genetic analysis revealed that the proband and his father both carried a heterozygous g.2736dupT variant of the AT gene. Bioinformatic analysis suggested that the variant may be pathogenic. CONCLUSION: The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene. The variant was unreported previously.


Asunto(s)
Deficiencia de Antitrombina III , Antitrombina III/genética , Deficiencia de Antitrombina III/genética , Análisis Mutacional de ADN , Pruebas Genéticas , Heterocigoto , Humanos , Masculino , Mutación , Linaje
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1253-1256, 2020 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-33179233

RESUMEN

OBJECTIVE: To explore the genetic basis of a patient presenting with dysmorphism, intellectual disability, psychomotor delay and hypoplasia of corpus callosum by using next generation sequencing. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his family members and subjected to exome sequencing. Suspected variants were verified with Sanger sequencing. RESULTS: The patient was found to carry a heterozygous c.1357delAinsGGA variant in exon 11 of the TCF4 gene, which was verified as de novo by Sanger sequencing. The variant may result in a truncated protein and affect its function. CONCLUSION: The heterozygous c.1357delAinsGGA variant the TCF4 gene probably underlies the disease in the proband.


Asunto(s)
Hiperventilación/genética , Discapacidad Intelectual/genética , Factor de Transcripción 4/genética , Facies , Pruebas Genéticas , Humanos , Masculino
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1265-1268, 2020 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-33179236

RESUMEN

OBJECTIVE: To explore the genetic cause of a patient suspected for congenital ectodermal dysplasia with repeated hyperthermia and to assess the reproductive risk for his family. METHODS: Medical whole-exome sequencing (WES) were used to detect single-nucleotide variations and low-coverage massively parallel copy number variation sequencing (CNV-seq) were employed to verify suspected CNVs. PCR and real-time quantitative PCR were applied to confirm the deletion of EDA gene. RESULTS: The results of WES suggested that the patient carried a hemizygous deletion for chrX:69 243 016-69 395 730. CNV-seq indicated that the patient carried a deletion of approximately 0.12 Mb on Xq13.1, which encompassed the EDA gene. The PCR results confirmed that there was a hemizygous deletion of exons 3 to 8 of the EDA gene. The same deletion was not found in his mother. CONCLUSION: The congenital ectodermal dysplasia of the patient may be attributed to deletion of exons 3 to 8 of the EDA gene, which could be de novo or derive from germline mosaicism of his mother. The WES and CNV-seq are of great value for the diagnosis of rare diseases.


Asunto(s)
Variaciones en el Número de Copia de ADN , Displasia Ectodérmica , Secuenciación del Exoma Completo , Displasia Ectodérmica/genética , Ectodisplasinas/genética , Exones , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mosaicismo , Eliminación de Secuencia
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1272-1275, 2020 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-33179238

RESUMEN

OBJECTIVE: To explore the clinical phenotype and pathogenic variants in a Chinese pedigree affected with Smith-Lemli-Opitz syndrome. METHODS: Peripheral blood samples were collected from five members, including two affected ones, from the pedigree for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing as well as reverse transcription sequencing at the RNA level. RESULTS: The proband and another affected child from the pedigree showed mental retardation, dyskinesia, microcephaly, micrognathia, anteverted nares, and 2/3 toe syndactyly. The proband also had hypospadia, single upper incisor, and lower serum cholesterol level. Both children were found to harbor a paternally derived c.278C>T (p.T93M) variant and a maternally derived c.907G>A (p.G303R) variant of the DHCR7 gene. Both were known pathogenic mutations. CONCLUSION: The compound heterozygous mutations of c.278C>T (p.T93M) and c.907G>A (p.G303R) of the DHCR7 gene probably underlay the disease in this pedigree. Above finding has enabled early diagnosis and treatment of Smith-Lemli-Opitz syndrome.


Asunto(s)
Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Síndrome de Smith-Lemli-Opitz , Niño , Pruebas Genéticas , Humanos , Linaje , Fenotipo , Síndrome de Smith-Lemli-Opitz/diagnóstico , Síndrome de Smith-Lemli-Opitz/genética
10.
Neurol Neurochir Pol ; 54(5): 364-365, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33135151

RESUMEN

INTRODUCTION: Antos et al. [7] have reported a case of suspected uniparental disomy leading to an initial erroneous diagnosis of Wilson's Disease on the basis of genetic testing. They discuss the usefulness of the 64Cu radioactive copper incorporation test as an often-overlooked diagnostic aid. CLINICAL REFLECTIONS: Wilson's Disease is difficult to diagnose because of its rarity, diverse clinical presentations, and the absence of a single fail-safe diagnostic test. The identification of mutations in the ATP7B gene has been an invaluable aid in the diagnosis, but genetic testing alone is not infallible, and should not be used as the sole diagnostic test in arriving at a diagnosis of Wilson's Disease. CLINICAL IMPLICATIONS: The diagnosis of Wilson's Disease must be based on a combination of findings that includes clinical history, clinical examination, and diagnostic testing. Genetic testing alone is insufficient.


Asunto(s)
Degeneración Hepatolenticular , Radioisótopos de Cobre , Pruebas Genéticas , Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/genética , Humanos
11.
BMC Med Genet ; 21(1): 195, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33008311

RESUMEN

BACKGROUND: Alagille syndrome is an autosomal dominant disorder usually caused by pathogenic variants of the JAG1 gene. In the past, cholestasis was a condition sine qua non for diagnosis of the syndrome. However, recent advancements in genetic testing have revealed that clinical presentations vary from lack of symptoms, to multiorgan involvement. Tetralogy of Fallot, the most frequent complex congenital heart defect in Alagille Syndrome, very rarely leads to renal failure requiring dialysis - there are only single reports of such cases in the literature, with none of them in Alagille Syndrome. CASE PRESENTATION: A 41-year-old woman suffering from cyanosis, dyspnea and plethora was admitted to the hospital. The patient suffered from chronic kidney disease and tetralogy of Fallot and had been treated palliatively with Blalock-Taussig shunts in the past; at admission, only minimal flow through the left shunt was preserved. These symptoms, together with impaired mental status and dysmorphic facial features, led to extensive clinical and genetic testing including whole exome sequencing. A previously unknown missense variant c.587G > A within the JAG1 gene was identified. As there were no signs of cholestasis, and subclinical liver involvement was only suggested by elevated alkaline phosphatase levels, the patient was diagnosed with incomplete Alagille Syndrome. End-stage renal disease required introduction of renal replacement therapy. Continuous ambulatory peritoneal dialysis was chosen and the patient's quality of life significantly increased. However, after refusal of further treatment, the patient died at the age of 45. CONCLUSIONS: Tetralogy of Fallot should always urge clinicians to evaluate for Alagille Syndrome and offer patients early nephrological care. Although tetralogy of Fallot rarely leads to end-stage renal disease requiring dialysis, if treated palliatively and combined with renal dysplasia (typical of Alagille Syndrome), it can result in severe renal failure as in the presented case. There is no standard treatment for such cases, but based on our experience, peritoneal dialysis is worth consideration. Finally, clinical criteria for the diagnosis of Alagille Syndrome require revision. Previously, diagnosis was based on cholestasis - however, cardiovascular anomalies are found to be more prevalent. Furthermore, the criteria do not include renal impairment, which is also common.


Asunto(s)
Síndrome de Alagille/terapia , Proteína Jagged-1/genética , Mutación Missense , Diálisis Peritoneal/métodos , Insuficiencia Renal Crónica/terapia , Tetralogía de Fallot/terapia , Adulto , Síndrome de Alagille/diagnóstico , Síndrome de Alagille/genética , Resultado Fatal , Femenino , Pruebas Genéticas , Humanos , Cuidados Paliativos/métodos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/genética , Tetralogía de Fallot/diagnóstico , Tetralogía de Fallot/genética
12.
BMC Med Genet ; 21(1): 193, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33008324

RESUMEN

BACKGROUND: Kabuki syndrome (KS) is a rare congenital condition with cardinal manifestations of typical facial features, developmental delays, skeletal anomalies, abnormal dermatoglyphic presentations, and mild to moderate intellectual disability. Pathogenic variants in two epigenetic modifier genes, KMT2D and KDM6A, are responsible for KS1 and KS2, respectively. CASE PRESENTATION: A Chinese girl had persistent neonatal hypoglycemia and Dandy-Walker variant. Whole-exome sequencing identified a novel single nucleotide deletion in KMT2D (NM_003482.3 c.12165del p.(Glu4056Serfs*10)) that caused frameshift and premature termination. The mutation was de novo. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this variant is considered pathogenic. The patient was diagnosed with KS by molecular testing. CONCLUSION: A single novel mutation in KMT2D was identified in a KS patients with hypoglycemia and Dandy-Walker variant in the neonatal stage. A molecular test was conducted to diagnose KS at an early stage.


Asunto(s)
Anomalías Múltiples/genética , Proteínas de Unión al ADN/genética , Síndrome de Dandy-Walker/genética , Cara/anomalías , Enfermedades Hematológicas/genética , Hipoglucemia/genética , Proteínas de Neoplasias/genética , Eliminación de Secuencia , Enfermedades Vestibulares/genética , Anomalías Múltiples/diagnóstico , Secuencia de Bases , Síndrome de Dandy-Walker/diagnóstico , Femenino , Pruebas Genéticas , Enfermedades Hematológicas/diagnóstico , Humanos , Hipoglucemia/diagnóstico , Recién Nacido , Homología de Secuencia de Ácido Nucleico , Enfermedades Vestibulares/diagnóstico , Secuenciación del Exoma Completo/métodos
13.
BMC Med Genet ; 21(1): 196, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33032550

RESUMEN

BACKGROUND: Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline mutations in two genes, SMAD4 and BMPR1A, have been identified to cause JPS. CASE PRESENTATION: Here, we report a germline heterozygous missense variant (c.299G > A) in exon 3 BMPR1A gene in a family with juvenile polyposis. This variant was absent from the population database, and concluded as de novo compared with the parental sequencing. Further sequencing of the proband's children confirmed the segregation of this variant with the disease, while the variant was also predicted to have damaging effect based on online prediction tools. Therefore, this variant was classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. CONCLUSIONS: Germline genetic testing revealed a de novo germline missense variant in BMPR1A gene in a family with juvenile polyposis. Identification of the pathogenic variant facilitates the cancer risk management of at-risk family members, and endoscopic surveillance is recommended for mutation carriers.


Asunto(s)
Poliposis Adenomatosa del Colon/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Mutación de Línea Germinal , Poliposis Intestinal/congénito , Mutación Missense , Síndromes Neoplásicos Hereditarios/genética , Poliposis Adenomatosa del Colon/diagnóstico , Adulto , Salud de la Familia , Femenino , Pruebas Genéticas , Heterocigoto , Humanos , Poliposis Intestinal/diagnóstico , Poliposis Intestinal/genética , Masculino , Síndromes Neoplásicos Hereditarios/diagnóstico , Linaje , Proteína Smad4/genética
14.
Nat Commun ; 11(1): 4093, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-33097703

RESUMEN

A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] = 0.8%), was associated with decreased ultradistal forearm BMD (P-value = 2.1 × 10-18), and increased osteoporosis (P-value = 4.2 × 10-5) and fracture risk (P-value = 1.6 × 10-5). The MEPE LoF association with BMD and fractures was further evaluated in 279,435 UK (MAF = 0.05%, heel bone estimated BMD P-value = 1.2 × 10-16, any fracture P-value = 0.05) and 375,984 Icelandic samples (MAF = 0.03%, arm BMD P-value = 0.12, forearm fracture P-value = 0.005). Screening for the MEPE LoF mutations before adulthood could potentially prevent osteoporosis and fractures due to the lifelong effect on BMD observed in the study. A key implication for precision medicine is that high-impact functional variants missing from the publicly available cosmopolitan panels could be clinically more relevant than polygenic risk scores.


Asunto(s)
Densidad Ósea/genética , Proteínas de la Matriz Extracelular/genética , Fracturas Óseas/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Glicoproteínas/genética , Fosfoproteínas/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Biología Computacional , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Genoma Humano , Humanos , Islandia , Masculino , Persona de Mediana Edad , Osteoporosis/genética
15.
Medicine (Baltimore) ; 99(41): e22497, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33031286

RESUMEN

RATIONALE: Paragangliomas (PGLs) are rare neuroendocrine tumors that are strongly influenced by genetics, and succinate dehydrogenase-deficient PGLs appear to constitute one of the most important categories. Interestingly, somatic PGLs only possess genomic alterations involving the SDHB and SDHD subunits, and no SDHA alterations have been described. Here, we are presenting the clinical and genetic analyses of 2 cases with the first somatic SDHA variant identified in PGLs. PATIENT CONCERNS: Here, we reported 2 family members with the diagnosis of PGL. Patient 1 is a 55-year-old woman with a functionally perigastric PGL that co-occurred with a gastric gastrointestinal stromal tumor (GIST), and patient 2 is a 43-year-old woman with a nonfunctionally pericardial PGL, who was the younger sister of the first patient. DIAGNOSES: Imaging surveys of the 2 cases depicted the presence of a perigastric and a pericardial mass, respectively. A diagnosis of paragangliomas was established by immunohistochemistry (IHC). INTERVENTIONS: Both patients underwent single-stage resection of the lesion after preoperative oral α-adrenoceptor therapy for 2 weeks. We later performed comprehensive genomic profiling on the tumor samples, including PGL and GIST from patient 1 and PGL from patient 2, and searched for novel actionable mutations, including in all succinate dehydrogenase subunits, as the IHC results were negative for SDHB. OUTCOMES: Both patients had an uneventful recovery after surgery and the sequencing showed a novel somatic variant in the SDHA gene on chromosome 5q11 (c.1945_1946delTT). Regular follow-up with biochemical testing and image studies showed no evidence of recurrence after a year for patient 1 and 6 years for patient 2. LESSONS: PGLs often lead to considerable diagnostic difficulty due to their multiple anatomical locations and variable symptoms, as presented by our cases. The comprehensive use of images and plasma/urine catecholamine measurement can aid the diagnosis of PGLs. In addition, our findings also demonstrate the usefulness and importance of genetic analysis of SDHA mutations in patients exhibiting SDHB IHC-negative PGL. Additional studies utilizing comprehensive genomic profiling are needed to identify the group of PGLs harboring this SDHA genomic alteration.


Asunto(s)
Complejo II de Transporte de Electrones/genética , Tumores del Estroma Gastrointestinal/genética , Neoplasias Primarias Múltiples/genética , Paraganglioma Extraadrenal/genética , Neoplasias Gástricas/genética , Adulto , Femenino , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/patología , Pruebas Genéticas , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mutación , Paraganglioma Extraadrenal/diagnóstico , Paraganglioma Extraadrenal/patología , Hermanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología
16.
Acta Gastroenterol Belg ; 83(3): 393-397, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33094585

RESUMEN

BACKGROUND/AIMS: In childhood, clinical presentation of intes- tinal polyps is variable. Painless rectal red blood loss is the most common presenting sign. Most polyps are sporadic, isolated and benign. However, it is important to correctly identify exceptions. Rare inherited polyposis syndromes need to be recognized because of their increased risk of intestinal and extra-intestinal malignancies. Furthermore, a correct diagnosis and treatment of rare gastro-intestinal malignancies is crucial. METHODS: Between 2016 and 2018 we encountered 4 different types of intestinal polyps. A database search was performed and patient files were checked for clinical manifestations and histo- pathology. Literature was searched to recapitulate red flags for these syndromes, probability of underlying genetic disorders and diagnostic criteria. RESULTS: Between 2016 and 2018, 28 patients presented at the Ghent University Hospital with 30 juvenile polyps. Furthermore, we diagnosed juvenile polyposis syndrome, Li Fraumeni syndrome and familial adenomatous polyposis (FAP) in 1 patient each, whilst 2 FAP patients were in follow-up. Each of these diagnoses has a different lifetime risk of (extra)-intestinal malignancy and requires a different approach and follow-up. Histopathology and genetic testing play an important role in identifying these syndromes in pediatric patients. CONCLUSION: Although most intestinal polyps in childhood are benign juvenile polyps that require no follow-up, rare inherited syndromes should be considered and correctly diagnosed since adequate follow-up is necessary to reduce morbidity and mortality from both gastrointestinal and extraintestinal complications and malignancies.


Asunto(s)
Poliposis Adenomatosa del Colon , Poliposis Intestinal , Pólipos Intestinales , Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/genética , Adolescente , Niño , Pruebas Genéticas , Humanos , Poliposis Intestinal/diagnóstico , Poliposis Intestinal/genética , Pólipos Intestinales/diagnóstico , Pólipos Intestinales/genética
17.
PLoS One ; 15(10): e0239714, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33052909

RESUMEN

The general public is increasingly aware of the role of genes in causing depression. Recent studies have begun uncovering unintended negative consequences of learning about a person's genetic susceptibility to disorders. Because people tend to believe that genes determine one's identity, having genes related to a disorder can be misinterpreted as equivalent to having the disorder. Consequently, learning that a person is genetically predisposed to depression can make people misremember mild depression as more severe. Participants across three experiments read a target vignette about a character displaying mild depressive symptoms, while descriptions of the character's genetic susceptibility to depression were experimentally manipulated. Participants then read a foil vignette describing a character with more severe depressive symptoms. Afterwards, participants who had learned that the target character was genetically predisposed to depression were comparatively more likely to misremember the target symptoms as being severe, when in fact they were mild. This pattern of results was obtained among both laypeople (Experiments 1 and 2) and practicing master's-level, but not doctoral-level, mental health clinicians (Experiment 3). Given that depression is diagnosed primarily based on a person's memory of depressive symptoms, the current findings suggest that genetic information about depression may lead to over-diagnosis of depression.


Asunto(s)
Depresión/genética , Predisposición Genética a la Enfermedad/psicología , Pruebas Genéticas/ética , Adulto , Depresión/metabolismo , Depresión/psicología , Trastorno Depresivo/psicología , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Aprendizaje , Masculino , Memoria , Prejuicio/psicología
18.
Stud Health Technol Inform ; 273: 129-135, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-33087602

RESUMEN

In this paper, we describe a strategy for the development of a genetic analysis comprehensive representation. The primary intention is to ensure the available utilization of genetic analysis results in clinical practice. The system is called Personnel Genetic Card (PGC), and it is developed in cooperation of CIIRC CTU in Prague and the Mediware company. Nowadays, genetic information is more and more part of medicine and life quality services (e.g. nutritional consulting). Therefore, there is necessary to bind genetic information with the clinical phenotype, such as drug metabolism or intolerance to various substances. We proposed a structured form of the record, where we utilize the LOINC® standard to identify genetic test parameters, and several terminology databases for representing specific genetic information (e.g. HGNC, NCBI RefSeq, NCBI dbNSP, HGVS). Further, there are also several knowledge databases (PharmGKB, SNPedia, ClinVar) that collect interpretation for genetic analysis results. In the results of this paper, we describe our idea in the structure and process perspective. The structural perspective includes the representation of the analysis record and its binding with the interpretations. The process perspective describes roles and activities within the PGC system use.


Asunto(s)
Pruebas Genéticas , Información Personal , Bases de Datos Genéticas , Logical Observation Identifiers Names and Codes , Fenotipo
19.
Medicine (Baltimore) ; 99(40): e21965, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019389

RESUMEN

BACKGROUND: The epidermal growth factor receptor (EGFR) mutation status related to the treatment approach for advanced non-small cell lung cancer (NSCLC) patients. This study aimed to evaluate the diagnostic accuracy of peripheral blood circulating tumor DNA (ctDNA) in EGFR mutated advanced NSCLC patients. METHOD: The related database was systematically searched with keywords until January 19, 2020. Studies contained the histopathological and cytological advanced NSCLC samples were included, and the diagnostic data were recorded for calculating sensitivity and specificity. I statistics were used for detecting heterogeneity across studies, and the meta-regression was performed to seek the source of heterogeneity. RESULT: A total of 32 studies with 4527 advanced NSCLC patients were included in our meta-analysis. Among them, 87% of the patients were diagnosed as stage IV. The pooled sensitivity of peripheral blood ctDNA was 0.70 (95% CI: 0.63-0.75, I = 81.76) and the pooled specificity was 0.98 (95% CI: 0.96-0.99, I = 88.33). The meta-regression showed that the prospective study design and the ARMS detection method were the main source of heterogeneity for sensitivity (P < .05), and the publication country (Asia or non-Asia) was the main source of heterogeneity for specificity (P < .01). CONCLUSION: ctDNA biopsy has high specificity and diagnostic accuracy in detection of EGFR mutation in advanced NSCLC patients. When the ctDNA gene test result is negative, we should fully consider the risk of missed diagnosis, and further tissue biopsy is still needed to undertake.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , ADN Tumoral Circulante/sangre , Neoplasias Pulmonares/genética , Biomarcadores/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Receptores ErbB/sangre , Femenino , Pruebas Genéticas , Humanos , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , Mutación , Estudios Prospectivos , Sensibilidad y Especificidad
20.
Arch Pathol Lab Med ; 144(10): 1193-1198, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33002154

RESUMEN

CONTEXT.­: Convenience, avoidance of doctor's appointments, curiosity, and the desire to take control of one's health are driving interest toward direct-to-consumer (DTC) testing. DTC is laboratory testing that is initiated by the consumer without a physician order. The results are reported back directly to the consumer. DTC testing is an exciting addition to the traditional healthcare model for consumers who want knowledge of their health status and disease risk, ancestry, and their body's expected response to certain medications based on their genotype. OBJECTIVES.­: To discuss the perceived and potential benefits and risks involved in DTC testing. DATA SOURCES.­: Recent published literature on DTC testing. CONCLUSIONS.­: The benefits of DTC testing are enticing and are driving the DTC testing market. Consumers must weigh the perceived benefits with the potential risks, including privacy concerns, the possibility of receiving confusing health information, and/or information that could generate unexpected emotions, misdiagnosis, and over-testing.


Asunto(s)
Pruebas Dirigidas al Consumidor , Confidencialidad , Pruebas Genéticas , Humanos , Medición de Riesgo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA