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1.
Bratisl Lek Listy ; 120(9): 699-702, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475558

RESUMO

OBJECTIVES: The aim of our study is to demonstrate a causal link between two distinct diagnoses, the hereditary hearing loss, and the sudden sensorineural hearing loss. BACKGROUND: Sudden sensorineural hearing loss is an emergency condition in otolaryngology and a rare diagnosis in childhood. Most often it only affects one ear and its cause remains unknown. METHODS: We present a clinical study of a 10-year-old female patient presenting with bilateral sudden sensorineural hearing loss analyzed by Sanger sequencing of the GJB2 gene. RESULTS: The subject was referred to the hospital for bilateral sudden hearing loss which developed 3 days before the admission. Audiometric testing confirmed bilateral asymmetric sensorineural hearing loss. All routine diagnostic procedures including MRI and CT imaging showed normal results. She was treated with intravenous and intratympanic corticosteroids followed by hyperbaric oxygen therapy with partial hearing recovery in one ear. DNA analysis of the GJB2 gene identified biallelic c.35delG deletion. The subject had no other affected family members and her auditory development to that time was normal. CONCLUSION: Our finding extends the knowledge on phenotype variability in GJB2 variants. We suggest considering genetic testing in pediatric cases of bilateral sudden sensorineural hearing loss (Tab. 1, Fig. 4, Ref. 24).


Assuntos
Perda Auditiva Neurossensorial/genética , Perda Auditiva Súbita/genética , Criança , Conexinas/genética , Análise Mutacional de DNA , Feminino , Humanos , Deleção de Sequência
2.
Pol J Pathol ; 70(2): 115-126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556562

RESUMO

Ovarian cancer (OC) is the most lethal among gynecologic malignancies worldwide. Unfortunately, in around 70% of cases cancer is diagnosed in late stages (III-IV) which decreases the 5-year survival rate to 25%. The standard of care in ovarian cancer is debulking surgery followed by chemotherapy regimens based on platinum salts. Since 2014 PARP inhibitors became available for OC patients with germline or/and somatic mutations in BRCA1/2, including maintenance therapy. BRCA1/2 Next Generation Sequencing (NGS)-based analysis of formalin-fixed paraffin-embedded (FFPE) ovarian cancer samples becomes the standard of care. The aim of the present study was to evaluate the frequency of mutations in 201 unselected ovarian cancer tissues using the NGS method. In total, pathogenic mutations in both genes were detected in 24% (49/201) of the ovarian cancer cases tested. For 41 patients the results of testing of DNA isolated from blood sample revealed that 17% (35/201) mutations were germline origin, whereas 3% (6/201) mutations were somatic. In 4% (8/201) cases blood sample was inaccessible. The presence of pathogenic mutations was correlated with younger age at diagnosis and serous subtype. Close cooperation between many specialists (gynecologist, pathologist, oncologist, clinical genetics and molecular biologist) is indispensable for efficient and on-time BRCA1/2 ovarian tumor tissue testing.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/genética , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
3.
Medicina (B Aires) ; 79(4): 265-270, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487245

RESUMO

Malignant melanoma (MM) is the more aggressive form of skin cancer with a mortality rate in Argentina 1997-2001 = 1.1/100 000 in men and 0.6 in women. BRAF proto-oncogene is focus of intense research; its mutation is one of the main tumor promoters and occurs in approximately 50% of MM. Several drugs with clinical activity on BRAF mutations have been approved. The aim of the study is to evaluate the mutational status of BRAF (exon 15) in cutaneous MM biopsies and its relationship with histopathological characteristics. We carried out an observational, retrospective study of samples fixed in formaldehyde and paraffin embedded; reviewing age, sex, diagnosis, histopathological data, tumor size and percentage, viability for molecular analysis and melanin presence. We evaluated BRAF mutations with PCR/Sanger sequencing. For statistics we used Student's t test, Chi square, Wilcoxon and Fisher's exact test. We were able to purify and sequence 76% (38/49) samples, 13/38 (34%) from women and 25/38 (66%) from men, the median age being 70 years. Most frequent location: thorax 14/35 (40%). Histological type: Superficial spreading 18/38 (47%). Clark's levels, 11/38 (29%): I-II and 27/38 (71%): III, IV and V. Breslow's median: 1.6 mm. Radial growth phase 11/38 (29%) and 27/38 (71%) vertical. Presented mutations 16/38 (42%). As reported by other authors, no association was found between the mutational state of exon 15 and clinical or histopathological parameters.


Assuntos
Melanoma/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Neoplasias Cutâneas/patologia
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 857-861, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515775

RESUMO

OBJECTIVE: To carry out mutation analysis for patients with myelodysplastic syndromes (MDS) and a normal karyotype. METHODS: Targeted capture and next-generation sequencing (NGS) was carried out using a customized 49-gene panel. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutations were detected by PCR and Sanger sequencing. RESULTS: Sixty-two patients (80.5%) were found to harbor at least one mutation. Each patient has carried 2.21 mutations in average. Coexistence of ≥ 3 mutations was common (43.7%). The most commonly mutated genes were RUNX1 (23.4%, 18/77), ASXL1 (18.2%, 14/77), NPM1 (15.6%, 12/77), U2AF1 (15.6%, 12/77), DNMT3A (11.7%, 9/77). Patients with SF3B1 mutations were significantly older than those with ASXL1 mutations (P=0.023). Mutations of the DNMT3A gene were significantly associated with the blood platelet level compared with BCOR mutations (P=0.02). No significant difference was found in the number and rate of mutations between those under or above 60-year-old. Among 67 patients with clinical follow-up, 20 (29.8%) has transformed to acute myeloid leukemia, and the time of transformation has ranged from 1 to 44 months, with a average of 5.3 months. RUNX1, U2AF1 and FLT3 mutations are associated with leukemic transformation. CONCLUSION: Coexistence of ≥ 3 mutations are frequent among patients with normal-karyotype MDS. Certain mutations are associated with age and leukemic transformation.


Assuntos
Análise Mutacional de DNA , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Fatores Etários , Humanos , Cariótipo , Pessoa de Meia-Idade , Mutação , Prognóstico
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 862-865, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515776

RESUMO

OBJECTIVE: To screen for pathogenic variants in the coding regions of STK11 gene among Chinese patients with Peutz-Jeghers syndrome (PJS). METHODS: Peripheral blood samples were collected from 64 patients. The coding regions of the STK11 gene were detected by PCR and Sanger sequencing. RESULTS: Fourty-eight patients were found to harbor STK11 gene variants, which included 39 types of variants consisting of missense, nonsense, insertional, deletional and splice site variants. Among 64 PJS patients, the detection rate of point variants was 75.00% (48/64), of which missense variants accounted for 29.17% (14/48), nonsense variants accounted for 29.17%(14/48), insertion variants accounted for 2.08% (1/48), deletional variants accounted for 10.42% (5/48), and splice site variants accounted for 29.17% (14/48). The detection rates of sporadic cases and those with a family history were 71.8% (28/39) and 80.0% (20/25), respectively. Two variants (c.250A>T, c.580G>A) occurred in 3 PJS probands. Thirteen variants were unreported previously and were considered to be pathogenic. CONCLUSION: The detection rate of variants among Chinese PJS patients is similar to that of other countries. A number of novel common variant sites were discovered, which enriched the spectrum of PJS-related variants.


Assuntos
Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Grupo com Ancestrais do Continente Asiático , China , Análise Mutacional de DNA , Humanos
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 897-900, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515785

RESUMO

OBJECTIVE: To explore the genetic basis for a case of recurrent fetal congenital hydrocephalus. METHODS: Next-generation sequencing was carried out for the fetus, the gravida and two of her sisters. RESULTS: The fetus was found to harbor a c.1765T>C (p.Tyr589His) mutation in exon 14 of the L1CAM gene, which was derived from the gravida. CONCLUSION: Male fetuses with recurrent hydrocephalus should be subjected to testing of the L1CAM gene to facilitate genetic counseling and prenatal diagnosis.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Hidrocefalia/genética , Molécula L1 de Adesão de Célula Nervosa/genética , Análise Mutacional de DNA , Feminino , Feto , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Hidrocefalia/diagnóstico , Masculino , Mutação , Linhagem , Gravidez
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 901-904, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515786

RESUMO

OBJECTIVE: To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. METHODS: Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. RESULTS: The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c.92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. CONCLUSION: The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.


Assuntos
Afibrinogenemia/genética , Fibrinogênio/genética , Afibrinogenemia/congênito , Análise Mutacional de DNA , Feminino , Humanos , Mutação , Linhagem , Fenótipo
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 905-909, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515787

RESUMO

OBJECTIVE: To detect mutation of LBR gene in a pedigree affected with Pelger-Huёt anomaly (PHA) and to explore its clinical characteristics. METHODS: Genomic DNA was extracted from the pedigree and healthy controls. The 14 exons of the LBR gene were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified in other family members and 100 healthy controls. Polyphen-2 and SIFT software were used to predict the effect of the mutation, and Swiss-model software was used to simulate the protein structure. RESULTS: Three patients were found to carry a c.893G>A mutation in exon 8 of the LBR gene, which resulted in substitution of the 298th amino acid residue glycine by glutamic acid (p.Gly298Glu). The same mutation was not found in healthy family members and 100 healthy controls. The mutation was predicted to be damaging. Bioinformatic simulation showed the mutation has altered the 3D structure of the LBR protein. CONCLUSION: The c.893G>A (p.Gly298Glu) mutation in the LBR gene probably underlies the PHA in this pedigree and has enriched the spectrum of LBR gene mutations.


Assuntos
Anomalia de Pelger-Huët/genética , Receptores Citoplasmáticos e Nucleares/genética , Estudos de Casos e Controles , Análise Mutacional de DNA , Éxons , Humanos , Mutação , Linhagem , Reação em Cadeia da Polimerase
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 930-934, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515793

RESUMO

OBJECTIVE: To detect potential mutations of HEXB gene in an infant with Sandhoff disease (SD). METHODS: Genomic DNA was extracted from peripheral blood sample of the infant. All coding exons (exons 1 to 14) and splicing sites of the HEXB gene were subjected to PCR amplification and direct sequencing.PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. PubMed BLAST CD-search was performed to identify functional domains destroyed by thecandidate mutations. Impact of the mutations was analyzed with software including PolyPhen-2, Mutation Taster and SIFT. Whole-exome sequencing was carried out to identify additional mutations. RESULTS: The infant was found to carry compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) of the HEXB gene. The c.1389C>G (p.Tyr463*) mutation may lead to destruction of two functional domains in ß subunit of the Hex protein. The c.1652G>A(p.Cys551Tyr) mutation, unreported previously,was predicted to be probably damaging by Bioinformatic analysis. CONCLUSION: Compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) in the HEXB gene probably underlie the disease in this patient.


Assuntos
Doença de Sandhoff/genética , Cadeia beta da beta-Hexosaminidase/genética , Análise Mutacional de DNA , Éxons , Heterozigoto , Humanos , Lactente , Mutação , Reação em Cadeia da Polimerase
10.
BMC Ophthalmol ; 19(1): 191, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438893

RESUMO

BACKGROUND: To investigate the efficacy and safety of repeated phototherapeutic keratectomies (PTKs) during long-term treatment for corneal dystrophy (CD) in a Chinese pedigree carrying the R124L mutation in TGFBI. METHODS: This was a retrospective review of 20-year medical and genetic records involving five CD patients (10 eyes) from one pedigree. During this period, PTK was conducted for an eye when best-corrected distance visual acuity (BCDVA) reached > 1.0 (LogMAR), due to either primary or recurrent opacities in the cornea. All PTKs were performed by 193-nm excimer laser with or without creation of epithelial flaps. For each eye, routine measurements were conducted for the number of PTKs during follow-up, mean time to recurrence, and BCDVA pre- and post- every PTK (measurements within 3 months from each PTK). Corneal thicknesses measured after the last PTK and at the last visit were analyzed, and subjective satisfaction was assessed. RESULTS: Gene testing revealed an R124L mutation in TGFBI. During 19.60 ± 1.78 years of follow-up, PTKs were conducted twice for three eyes, three times for six eyes, and four times for one eye. After each PTK, effective visual acuity was maintained for 3.60 ± 1.12 years before significant recurrence. BCDVA improved significantly postoperatively than preoperatively for the first PTK for each eye (p < 0.001), as well as the second (p < 0.001) and third one (p < 0.001). After the last PTK and at the final visit, the thinnest corneal thickness was 371.50 ± 56.47 µm and 358.40 ± 101.11 µm, respectively. The average subjective satisfaction score was 8.60 ± 0.89. CONCLUSIONS: Multiple repeated PTKs were effective and safe in a long-term study of CD patients with an R124L mutation in TGFBI.


Assuntos
Córnea/cirurgia , Distrofias Hereditárias da Córnea/cirurgia , Proteínas da Matriz Extracelular/genética , Previsões , Lasers de Excimer/uso terapêutico , Mutação , Ceratectomia Fotorrefrativa/métodos , Fator de Crescimento Transformador beta/genética , Adulto , Idoso , China/epidemiologia , Córnea/patologia , Distrofias Hereditárias da Córnea/epidemiologia , Distrofias Hereditárias da Córnea/genética , DNA/genética , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Estudos Retrospectivos , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento , Acuidade Visual
11.
Presse Med ; 48(7-8 Pt 1): 816-824, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31439443

RESUMO

Diagnosis of mature B cell malignancies is highly multidisciplinary. Biological tools provide diagnostic, prognostic and theranostic information. Biological hematology allows considering mature B cell diseases from two perspectives : cellular and molecular approaches. Cytomorphology and flow cytometry are tools from cell hematology. Conventional cytogenetics, FISH and molecular biology are tools from molecular hematology. NGS is a new technique that could dramatically change diagnostic and therapeutic management of B cell malignancies in the near future. Integration of clinical, pathological and biological data allows for personalized management of these diseases.


Assuntos
Técnicas de Laboratório Clínico/métodos , Leucemia de Células B/diagnóstico , Linfoma de Células B/diagnóstico , Integração de Sistemas , Hibridização Genômica Comparativa/métodos , Citodiagnóstico/métodos , Análise Citogenética/métodos , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imunofenotipagem/métodos , Hibridização in Situ Fluorescente/métodos , Leucemia de Células B/genética , Leucemia de Células B/patologia , Linfoma de Células B/genética , Linfoma de Células B/patologia , Técnicas de Diagnóstico Molecular/métodos , Imagem Multimodal/métodos , Imagem Multimodal/tendências
12.
Presse Med ; 48(7-8 Pt 1): 832-841, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31444019

RESUMO

Lymphoplasmocytic lymphona with monoclonal lgM, rare. Median age at diagnosis 70 years old, frail population. Heterogenous clinic presentation. Molecular diagnosis with MYD88. Treatment required for symptomatic WM patients only. 1st line therapy: DRC. Input of targeted therapies (ibrutinib) for frail patients, maintenance effect.


Assuntos
Macroglobulinemia de Waldenstrom , Idade de Início , Idoso , Análise Mutacional de DNA/métodos , Idoso Fragilizado , Humanos , Técnicas de Diagnóstico Molecular/métodos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Fator 88 de Diferenciação Mieloide/genética , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/epidemiologia , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/terapia
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 757-760, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400121

RESUMO

OBJECTIVE: To identify pathogenic variations of EXT1 and EXT2 genes in two Chinese pedigrees affected with hereditary multiple exostosis (HME). METHODS: Genomic DNA was extracted from peripheral blood samples using a phenol-chloroform method. PCR and Sanger sequencing was conducted to amplify the exons and the flanking intronic regions of the EXT1 and EXT2 genes. RESULTS: DNA sequencing has revealed a heterozygous missense variation c.812A>G (p.Tyr271Cys) in the exon 1 of EXT1 in pedigree 1, and a heterozygous frameshift variation c.1431dup (p.Ser478Leufs*43) in the exon 6 of EXT1 in the proband from pedigree 2. Both variations have co-segregated with the disease phenotype, which was also consistent with previous report. CONCLUSION: Two heterozygous pathogenic variations underlying HME have been identified. The result has facilitated genetic counseling and prenatal diagnosis for the affected pedigrees.


Assuntos
Exostose Múltipla Hereditária/genética , N-Acetilglucosaminiltransferases/genética , Grupo com Ancestrais do Continente Asiático , Sequência de Bases , Análise Mutacional de DNA , Exostose Múltipla Hereditária/patologia , Mutação da Fase de Leitura , Humanos , Mutação de Sentido Incorreto , Linhagem
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 765-768, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400123

RESUMO

OBJECTIVE: To detect potential mutations of the PKHD1 gene in two pedigrees affected with infantile polycystic kidney disease. METHODS: Clinical data and peripheral venous blood samples were collected from the probands and their parents as well as fetal amniotic fluid cells. Genome DNA was extracted from the peripheral blood samples and amniotic fluid cells. Exons 32 and 61 of the PKHD1 gene were amplified with PCR and subjected to direct sequencing. RESULTS: The proband of pedigree 1 was found to carry c.4274T>G (p.Leu1425Arg) mutation in exon 32 and c.10445G>C (p.Arg3482Pro) mutation in exon 61 of the PKHD1 gene, which were inherited from her father and mother, respectively. The fetus has carried the c.4274T>G (p.Leu1425Arg) mutation. In pedigree 2, the wife and her husband had respectively carried a heterozygous c.5979_5981delTGG mutation and a c.9455delA mutation of the PKHD1 gene. No chromosomal aberration was found in the umbilical blood sample, but the genetic testing of their fetus was failed. Based on software prediction, all of the 4 mutations were predicted to be pathogenic. CONCLUSION: PKHD1 c.4274T>G (p.Leu1425Arg), c.10445G>C (p.Arg3482Pro), c.5979_5981delTGG and c.9455delA were likely to be pathogenic mutations. The results have facilitated genetic counseling and prenatal diagnosis for the two pedigrees.


Assuntos
Aconselhamento Genético , Doenças Renais Policísticas/diagnóstico , Doenças Renais Policísticas/genética , Diagnóstico Pré-Natal , Receptores de Superfície Celular/efeitos dos fármacos , Análise Mutacional de DNA , Feminino , Humanos , Mutação , Linhagem , Gravidez
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 821-825, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400137

RESUMO

OBJECTIVE: To explore the clinical, electrophysiological and imaging features of a patient with Krabbe disease caused by GALC mutation. METHODS: A comprehensive analysis including clinical investigation and genetic testing was carried out. RESULTS: The patient presented with peripheral neuropathy with electrophysiological anomaly suggestive of asymmetric demyelinating neuropathy. Brain imaging revealed leukoencephalopathy. Genetic analysis has identified compound heterozygous mutations in exons 5 and 11 of the GALC gene, namely c.461C>A and c.1244G>A. CONCLUSION: Krabbe disease is a group of disorders featuring substantial phenotypic heterogeneity. Genetic and enzyme testing has become indispensable for accurate diagnosis for this disease.


Assuntos
Galactosilceramidase/genética , Leucodistrofia de Células Globoides/genética , Doenças do Sistema Nervoso Periférico/etiologia , Análise Mutacional de DNA , Testes Genéticos , Humanos , Leucodistrofia de Células Globoides/complicações , Mutação
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 834-836, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400140

RESUMO

OBJECTIVE: To explore the clinical features and mutations of the TRPM6 gene in an infant featuring hypomagnesemia and secondary hypocalcemia. METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Targeted exome sequencing was carried out to screen the potential mutations. Suspected mutations were verified by Sanger sequencing. RESULTS: A novel homozygous c.5538delA (p.Q1846Qfs*2) mutation in the TRPM6 gene was identified in the proband, for which both of her parents were heterozygous carriers. CONCLUSION: The homozygous frameshift mutation of TRPM6 gene (c.5538delA) probably underlies the disease in the proband. The finding has expanded the mutation spectrum of TRPM6 gene.


Assuntos
Hipocalcemia/genética , Deficiência de Magnésio/congênito , Canais de Cátion TRPM/genética , Análise Mutacional de DNA , Feminino , Mutação da Fase de Leitura , Humanos , Lactente , Deficiência de Magnésio/genética
17.
J Cancer Res Clin Oncol ; 145(9): 2325-2333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317326

RESUMO

PURPOSE: Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated. METHODS: Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1-2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence. RESULTS: About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1-2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244-4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449-9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy. CONCLUSIONS: Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/metabolismo , Linfonodos/metabolismo , Mutação , Transcriptoma/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
18.
Science ; 365(6451): 318-319, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31346051
19.
J Pediatr Ophthalmol Strabismus ; 56: e45-e48, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31282960

RESUMO

Ectopia lentis is displacement of the lens from its original position. It can be inherited or acquired with isolated or systemic findings. The authors describe a 4-year-old girl with isolated ectopia lentis et pupillae caused by pathogenic variants in the ADAMTSL4 gene and discuss the molecular genetic work-up of individuals with ectopia lentis. [J Pediatr Ophthalmol Strabismus. 2019;56:e45-e48.].


Assuntos
Proteínas ADAMTS/genética , Algoritmos , DNA/genética , Ectopia do Cristalino/genética , Cristalino/diagnóstico por imagem , Mutação , Distúrbios Pupilares/genética , Proteínas ADAMTS/metabolismo , Pré-Escolar , Análise Mutacional de DNA , Ectopia do Cristalino/diagnóstico , Ectopia do Cristalino/metabolismo , Feminino , Humanos , Linhagem , Distúrbios Pupilares/diagnóstico , Distúrbios Pupilares/metabolismo , Tomografia de Coerência Óptica
20.
Medicine (Baltimore) ; 98(28): e16343, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305422

RESUMO

To estimate the BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma (PTC), and the diagnostic value of BRAFV600E mutation status in thyroid nodules with indeterminate TBSRTC categories.A total of 4875 consecutive samples for thyroid ultrasound-guided fine-needle aspiration cytology (FNAC) and BRAF mutation analysis were collected from patients at Jiangsu Province Hospital on Integration of Chinese and Western Medicine. Among all the cases, 314 underwent thyroidectomy. According to TBSRTC categories, FNAC was performed for a preoperative diagnosis. ROC of the subject was constructed to evaluate the diagnostic value of these 2 methods and their combination.BRAF mutation in FNAC of thyroid nodules occurred in 2796 samples (57.35%). Of 353 nodule samples from 314 patients with thyroid operation, 333 were pathologically diagnosed as PTC. Of these PTC patients, 292 (87.69%) were found to have BRAF mutation in their preoperative FNAC. In 175 cytologically indeterminate thyroid nodules, BRAF mutation identified 88% of PTC. According to ROC data, BRAF mutation testing had an obviously higher sensitivity (87.69%) and specificity (100.00%) than TBSRTC. Combining BRAF mutation testing and TBSRTC achieved the largest AUC (0.954). For 41 PTC with a negative BRAF mutation in preoperative evaluation, the repeated BRAF mutation testing found out 12 samples with BRAF mutation. The true BRAF mutation rate of Chinese PTC patients was 91.29%.Chinese patients with PTC have a higher frequency of BRAF mutation. The BRAF mutation testing affords a high diagnostic value in thyroid nodules with indeterminate cytology.


Assuntos
Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Criança , China , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/metabolismo , Sensibilidade e Especificidade , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Ultrassonografia de Intervenção , Adulto Jovem
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