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[PMID]:27776463
[Au] Autor:Li W; Zhou P; Zhao C; Zhang Y
[Ad] Endereço:a Department of Pediatrics , Xinqiao Hospital Third Military Medical University , Chongqing City , China.
[Ti] Título:A novel de novo mutation in the TSC2 gene in a Chinese patient with tuberous sclerosis complex.
[So] Source:J Neurogenet;30(3-4):285-287, 2016 Sep - Dec.
[Is] ISSN:1563-5260
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Tuberous sclerosis complex (TSC), a multisystem genetic syndrome, often affects the central nervous system. The age of onset of TSC ranges from 0 to 15 years. The clinical features manifest as a combination of seizures, mental retardation, facial angiofibroma, renal angiomyolipoma, and cardiac rhabdomyoma. Most cases of TSC are caused by mutations of the TSC1 or TSC2 genes. We characterized a Chinese patient with a novel de novo mutation in the TSC2 gene associated with the TSC detected by next-generation sequencing.
[Mh] Termos MeSH primário: Esclerose Tuberosa/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Grupo com Ancestrais do Continente Asiático/genética
Análise Mutacional de DNA
Feminino
Seres Humanos
Lactente
Mutação
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tumor Suppressor Proteins); 4JG2LF96VF (tuberous sclerosis complex 2 protein)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29261847
[Au] Autor:Bykhovskaya Y; Fardaei M; Khaled ML; Nejabat M; Salouti R; Dastsooz H; Liu Y; Inaloo S; Rabinowitz YS
[Ad] Endereço:Department of Surgery and Board of the Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States.
[Ti] Título:TSC1 Mutations in Keratoconus Patients With or Without Tuberous Sclerosis.
[So] Source:Invest Ophthalmol Vis Sci;58(14):6462-6469, 2017 Dec 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To test candidate genes TSC1 and TSC2 in a family affected by tuberous sclerosis complex (TSC) where proband was also diagnosed with bilateral keratoconus (KC) and to test the hypothesis that defects in the same gene may lead to a nonsyndromic KC. Methods: Next-generation sequencing of TSC1 and TSC2 genes was performed in a proband affected by TSC and KC. Identified mutation was confirmed by Sanger DNA sequencing. Whole exome sequencing (WES) was performed in patients with nonsyndromic KC. Sanger DNA sequencing was used to confirm WES results and to screen additional patients. RT-PCR was used to investigate TSC1 expression in seven normal human corneas and eight corneas from patients with KC. Various in silico tools were employed to model functional consequences of identified mutations. Results: A heterozygous nonsense TSC1 mutation g.132902703C>T (c.2293C>T, p.Gln765Ter) was identified in a patient with TSC and KC. Two heterozygous missense TSC1 variants g.132896322A>T (c.3408A>T, p.Asp1136Glu) and g.132896452G>A (c.3278G>A, p.Arg1093Gln) were identified in three patients with nonsyndromic KC. Two mutations were not present in The Genome Aggregation (GnomAD), The Exome Aggregation (ExAC), and 1000 Genomes (1000G) databases, while the third one was present in GnomAD and 1000G with minor allele frequencies (MAF) of 0.00001 and 0.0002, respectively. We found TSC1 expressed in normal corneas and KC corneas, albeit with various levels. Conclusions: Here for the first time we found TSC1 gene to be involved in bilateral KC and TSC as well as with nonsyndromic KC, supporting the hypothesis that diverse germline mutations of the same gene can cause genetic disorders with overlapping clinical features.
[Mh] Termos MeSH primário: DNA/genética
Ceratocone/genética
Mutação
Esclerose Tuberosa/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Adulto
Pré-Escolar
Análise Mutacional de DNA
Feminino
Seres Humanos
Ceratocone/complicações
Ceratocone/metabolismo
Masculino
Microscopia Acústica
Linhagem
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Tomografia Computadorizada por Raios X
Esclerose Tuberosa/complicações
Esclerose Tuberosa/diagnóstico
Proteínas Supressoras de Tumor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tumor Suppressor Proteins); 0 (tuberous sclerosis complex 1 protein); 9007-49-2 (DNA)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22819


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[PMID]:29217816
[Au] Autor:Catarino Santos S; Duarte L; Valério F; Constantino J; Pereira J; Casimiro C
[Ad] Endereço:Department of General Surgery, Centro Hospitalar Tondela-Viseu, Viseu, Portugal.
[Ti] Título:Wunderlich's Syndrome, or Spontaneous Retroperitoneal Hemorrhage, in a Patient with Tuberous Sclerosis and Bilateral Renal Angiomyolipoma.
[So] Source:Am J Case Rep;18:1309-1314, 2017 Dec 08.
[Is] ISSN:1941-5923
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Wunderlich's syndrome, or spontaneous non-traumatic retroperitoneal hemorrhage, can be a life-threatening event. Renal angiomyolipoma is a rare benign tumor that can occur sporadically, or in association with tuberous sclerosis. A case of spontaneous retroperitoneal hemorrhage in a patient with tuberous sclerosis and bilateral renal angiomyolipoma is presented. CASE REPORT A 33-year-old female Caucasian patient, with a known medical history of tuberous sclerosis, was admitted to hospital as an emergency, with right-sided abdominal pain. Abdominal computed tomography (CT) imaging showed bilateral renal tumors, consistent with bilateral renal angiomyolipoma. The larger tumor, involving the enlarged right kidney (24.0 cm in length), had a diameter of 21.0 cm and was associated with hemoperitoneum and retroperitoneal hemorrhage, and contrast 'blush' on CT confirmed arterial bleeding. An initial urgent exploratory laparotomy with renal packing was initially performed, but right nephrectomy was required for hemorrhage control. The patient was discharged from hospital on the 23rd postoperative day, without further complications. CONCLUSIONS This report describes a case of Wunderlich's Syndrome, or spontaneous retroperitoneal hemorrhage, in a patient with tuberous sclerosis and bilateral renal angiomyolipoma, presenting as an emergency. An early diagnosis and timely treatment are important in cases of retroperitoneal hemorrhage to prevent life-threatening complications.
[Mh] Termos MeSH primário: Angiomiolipoma/complicações
Hemorragia/etiologia
Neoplasias Renais/complicações
Espaço Retroperitoneal
Esclerose Tuberosa/complicações
[Mh] Termos MeSH secundário: Adulto
Angiomiolipoma/diagnóstico por imagem
Angiomiolipoma/patologia
Feminino
Seres Humanos
Neoplasias Renais/diagnóstico por imagem
Neoplasias Renais/patologia
Síndrome
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180109
[Lr] Data última revisão:
180109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:28457992
[Au] Autor:Capal JK; Bernardino-Cuesta B; Horn PS; Murray D; Byars AW; Bing NM; Kent B; Pearson DA; Sahin M; Krueger DA; TACERN Study Group
[Ad] Endereço:Department of Neurology MLC 2015, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address: Jamie.capal@cchmc.org.
[Ti] Título:Influence of seizures on early development in tuberous sclerosis complex.
[So] Source:Epilepsy Behav;70(Pt A):245-252, 2017 May.
[Is] ISSN:1525-5069
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Epilepsy is commonly seen in Tuberous Sclerosis Complex (TSC). The relationship between seizures and developmental outcomes has been reported, but few studies have examined this relationship in a prospective, longitudinal manner. The objective of the study was to evaluate the relationship between seizures and early development in TSC. METHODS: Analysis of 130 patients ages 0-36months with TSC participating in the TSC Autism Center of Excellence Network, a large multicenter, prospective observational study evaluating biomarkers predictive of autism spectrum disorder (ASD), was performed. Infants were evaluated longitudinally with standardized evaluations, including cognitive, adaptive, and autism-specific measures. Seizure history was collected continuously throughout, including seizure type and frequency. RESULTS: Data were analyzed at 6, 12, 18, and 24months of age. Patients without a history of seizures performed better on all developmental assessments at all time points compared to patients with a history of seizures and exhibited normal development at 24months. Patients with a history of seizures not only performed worse, but developmental progress lagged behind the group without seizures. All patients with a history of infantile spasms performed worse on all developmental assessments at 12, 18, and 24months. Higher seizure frequency correlated with poorer outcomes on developmental testing at all time points, but particularly at 12months and beyond. Patients with higher seizure frequency during infancy continued to perform worse developmentally through 24months. A logistic model looking at the individual impact of infantile spasms, seizure frequency, and age of seizure onset as predictors of developmental delay revealed that age of seizure onset was the most important factor in determining developmental outcome. CONCLUSIONS: Results of this study further define the relationship between seizures and developmental outcomes in young children with TSC. Early seizure onset in infants with TSC negatively impacts very early neurodevelopment, which persists through 24months of age.
[Mh] Termos MeSH primário: Deficiências do Desenvolvimento/fisiopatologia
Convulsões/fisiopatologia
Espasmos Infantis/fisiopatologia
Esclerose Tuberosa/fisiopatologia
[Mh] Termos MeSH secundário: Pré-Escolar
Deficiências do Desenvolvimento/epidemiologia
Deficiências do Desenvolvimento/psicologia
Feminino
Seres Humanos
Lactente
Estudos Longitudinais
Masculino
Estudos Prospectivos
Convulsões/epidemiologia
Convulsões/psicologia
Espasmos Infantis/epidemiologia
Espasmos Infantis/psicologia
Esclerose Tuberosa/epidemiologia
Esclerose Tuberosa/psicologia
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180109
[Lr] Data última revisão:
180109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:29232371
[Au] Autor:Brakemeier S; Vogt L; Adams L; Zukunft B; Diederichs G; Hamm B; Budde K; Makowski MR
[Ad] Endereço:Department of Nephrology and Medical Intensive Care, Charité, Berlin, Germany.
[Ti] Título:Treatment effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC).
[So] Source:PLoS One;12(12):e0189132, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML) have a high lifetime risk of acute bleeding. MTOR-inhibitors are a promising novel treatment for TSC-AML, however adequate response to therapy can be difficult to assess. Early changes in MRI signal may serve as a novel early indicator for a satisfactory response to mTOR-inhibitor therapy of AML. MATERIALS AND METHODS: Thirty-eight patients with the definite diagnosis of tuberous sclerosis receiving everolimus therapy and n = 19 patients without specific therapy were included. 1.5 Tesla MRI was performed including sequences with a selective fat suppression. Patients were investigated prior to the initiation of therapy (baseline) and after <3 months (n = 21 patients), 3 to 6 months (n = 32) and 18 to 24 months (n = 28). Signal and size changes of renal AMLs were assessed at all different timepoints. Signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and size of angiomyolipomas were evaluated. RESULTS: Signal changes in 273 AMLs were evaluated. A significant and strong decrease of the CNR of AMLs following the initiation of therapy was measured in the fat-suppressed MR sequence at all time points, compared to the baseline: From 7.41±6.98 to 3.84±6.25 (p ≤ 0.05p = 0.002), 3.36±6.93 (p<0.0001), and 2.50±6.68 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively. Also, a significant, however less pronounced, reduction of angiomyolipoma size in the different groups was measured (from baseline 2022.2±2657.7 mm2 to 1854.4±1670.9 mm2 (p = 0.009), 1875.5±3190.1 mm2 (p<0.001), and 1365.8 ± 1628.8 mm2 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively). No significant changes in CNR (p>0.05) and size (p>0.05) were measured in the control group. CONCLUSION: mTOR inhibitor therapy in TSC patients results in an early and pronounced fatty transformation of AMLs on MRI. Fatty transformation could represent a novel early indicator of response to therapy in this patient collective.
[Mh] Termos MeSH primário: Angiomiolipoma/complicações
Neoplasias Renais/complicações
Sirolimo/uso terapêutico
Serina-Treonina Quinases TOR/antagonistas & inibidores
Esclerose Tuberosa/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Angiomiolipoma/diagnóstico por imagem
Feminino
Seres Humanos
Neoplasias Renais/diagnóstico por imagem
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Razão Sinal-Ruído
Esclerose Tuberosa/complicações
Esclerose Tuberosa/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189132


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[PMID]:29029902
[Au] Autor:Wilder EG; Frieder J; Sulhan S; Michel P; Cizenski JD; Wright JM; Menter MA
[Ad] Endereço:Division of Dermatology, Baylor University Medical Center, Dallas, Texas.
[Ti] Título:Spectrum of orocutaneous disease associations: Genodermatoses and inflammatory conditions.
[So] Source:J Am Acad Dermatol;77(5):809-830, 2017 Nov.
[Is] ISSN:1097-6787
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The oral cavity and cutaneous organ systems share a close embryologic origin. Therefore, there are numerous dermatologic conditions presenting with concomitant oral findings of which the dermatologist must be aware. The second article in this continuing medical education series reviews inflammatory orocutaneous conditions and a number of genodermatoses. It is essential for dermatologists to be familiar with oral cavity manifestations associated with dermatologic diseases for prompt diagnosis, management, and appropriate referral to stomatology and dentistry.
[Mh] Termos MeSH primário: Doenças Genéticas Inatas/genética
Predisposição Genética para Doença/epidemiologia
Doenças da Boca/genética
Dermatopatias/genética
[Mh] Termos MeSH secundário: Doença de Darier/epidemiologia
Doença de Darier/genética
Doença de Darier/fisiopatologia
Educação Médica Continuada
Epiderme/patologia
Feminino
Doenças Genéticas Inatas/epidemiologia
Doenças Genéticas Inatas/fisiopatologia
Seres Humanos
Incidência
Masculino
Doenças da Boca/epidemiologia
Doenças da Boca/fisiopatologia
Mucosa Bucal/patologia
Prognóstico
Doenças Raras
Medição de Risco
Dermatopatias/epidemiologia
Dermatopatias/fisiopatologia
Neoplasias Cutâneas/epidemiologia
Neoplasias Cutâneas/genética
Neoplasias Cutâneas/fisiopatologia
Esclerose Tuberosa/epidemiologia
Esclerose Tuberosa/genética
Esclerose Tuberosa/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171015
[St] Status:MEDLINE


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[PMID]:28979625
[Au] Autor:Menany M; Khnaba S; Radouane B; Jidal M; Amil T; Saouab R
[Ad] Endereço:Department of Radiology, Military Hospital, Ibn Sina CHU, Rabat, Morocco.
[Ti] Título:Giant bilateral angiomyolipomas with spontaneous hemorrhage and inferior vena cava thrombosis in a patient with tuberous sclerosis.
[So] Source:Pan Afr Med J;27:223, 2017.
[Is] ISSN:1937-8688
[Cp] País de publicação:Uganda
[La] Idioma:eng
[Ab] Resumo:Renal angiomyolipomas are rare type of benign renal neoplasm. They are composed of vascular, smooth and fat elements and can be associated to phacomatosis as Tuberous Sclerosis disease. Symptomatic presentation is most frequently spontaneous retroperitoneal hemorrhage, which can be fatal. The risk of bleeding is proportional to the size of the lesion (>4 cm of diameter). Typical angiomyolipomas are benign but may have alarming properties: nuclear pleomorphism and mitotic activity, extension into the vena cava, and spread to regional lymph nodes without malignant progression. We report a Computed Tomography finding of a rare giant bilateral angiomyolipomas with spontaneous hemorrhage and inferior vena cava thrombus in a patient with tuberous sclerosis, emphasizing the importance of imagery in the positive and etiologic diagnosis.
[Mh] Termos MeSH primário: Angiomiolipoma/diagnóstico
Neoplasias Renais/diagnóstico
Veia Cava Inferior/patologia
Trombose Venosa/etiologia
[Mh] Termos MeSH secundário: Adulto
Angiomiolipoma/complicações
Angiomiolipoma/diagnóstico por imagem
Feminino
Hemorragia/etiologia
Seres Humanos
Neoplasias Renais/complicações
Neoplasias Renais/diagnóstico por imagem
Espaço Retroperitoneal/patologia
Tomografia Computadorizada por Raios X
Esclerose Tuberosa/patologia
Veia Cava Inferior/diagnóstico por imagem
Trombose Venosa/diagnóstico por imagem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.11604/pamj.2017.27.223.8379


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[PMID]:28968464
[Au] Autor:Rosset C; Vairo F; Bandeira IC; Correia RL; de Goes FV; da Silva RTB; Bueno LSM; de Miranda Gomes MCS; Galvão HCR; Neri JICF; Achatz MI; Netto CBO; Ashton-Prolla P
[Ad] Endereço:Laboratório de Medicina Genômica - Centro de Pesquisa Experimental - Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
[Ti] Título:Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis.
[So] Source:PLoS One;12(10):e0185713, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by the development of multiple hamartomas in many organs and tissues. It occurs due to inactivating mutations in either of the two genes, TSC1 and TSC2, following a second hit in a tumor suppressor gene in most hamartomas. Comprehensive screening for mutations in both the TSC1 and TSC2 loci has been performed in several cohorts of patients and a broad spectrum of pathogenic mutations have been described. In Brazil, there is no data regarding incidence and prevalence of tuberous sclerosis and mutations in TSC1 and TSC2. We analyzed both genes in 53 patients with high suspicion of tuberous sclerosis using multiplex-ligation dependent probe amplification and a customized next generation sequencing panel. Confirmation of all variants was done by the Sanger method. We identified 50 distinct variants in 47 (89%) of the patients. Five were large rearrangements and 45 were point mutations. The symptoms presented by our series of patients were not different between male and female individuals, except for the more common occurrence of shagreen patch in women (p = 0.028). In our series, consistent with other studies, TSC2 mutations were associated with a more severe phenotypic spectrum than TSC1 mutations. This is the first study that sought to characterize the molecular spectrum of Brazilian individuals with tuberous sclerosis.
[Mh] Termos MeSH primário: Família
Predisposição Genética para Doença
Esclerose Tuberosa/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Brasil
Feminino
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Seres Humanos
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Tumor Suppressor Proteins); 0 (tuberous sclerosis complex 1 protein); 4JG2LF96VF (tuberous sclerosis complex 2 protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185713


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[PMID]:28854430
[Au] Autor:Thibodeau ML; Steinraths M; Brown L; Zong Z; Shomer N; Taubert S; Mungall KL; Ma YP; Mueller R; Birol I; Lehman A
[Ad] Endereço:Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
[Ti] Título:Genomic and Cytogenetic Characterization of a Balanced Translocation Disrupting NUP98.
[So] Source:Cytogenet Genome Res;152(3):117-121, 2017.
[Is] ISSN:1424-859X
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:A 41-year-old Asian woman with bilateral renal angiomyolipomas (AML) was incidentally identified to have a balanced translocation, 46,XX,t(11;12)(p15.4;q15). She had no other features or family history to suggest a diagnosis of tuberous sclerosis. Her healthy daughter had the same translocation and no renal AML at the age of 3 years. Whole-genome sequencing was performed on genomic maternal DNA isolated from blood. A targeted de novo assembly was then conducted with ABySS for chromosomes 11 and 12. Sanger sequencing was used to validate the translocation breakpoints. As a result, genomic characterization of chromosomes 11 and 12 revealed that the 11p breakpoint disrupted the NUP98 gene in intron 1, causing a separation of the promoter and transcription start site from the rest of the gene. The translocation breakpoint on chromosome 12q was located in a gene desert. NUP98 has not yet been associated with renal AML pathogenesis, but somatic NUP98 alterations are recurrently implicated in hematological malignancies, most often following a gene fusion event. We also found evidence for complex structural events involving chromosome 12, which appear to disrupt the TDG gene. We identified a TDGP1 partially processed pseudogene at 12p12.1, which adds complexity to the de novo assembly. In conclusion, this is the first report of a germline constitutional structural chromosome rearrangement disrupting NUP98 that occurred in a generally healthy woman with bilateral renal AML.
[Mh] Termos MeSH primário: Angiomiolipoma/genética
Cromossomos Humanos Par 11/genética
Cromossomos Humanos Par 12/genética
Neoplasias Renais/genética
Complexo de Proteínas Formadoras de Poros Nucleares/genética
Translocação Genética
[Mh] Termos MeSH secundário: Adulto
Amniocentese
Análise Citogenética/métodos
Feminino
Proteínas Ligadas por GPI/genética
Estudo de Associação Genômica Ampla
Genômica/métodos
Seres Humanos
Peptídeos e Proteínas de Sinalização Intercelular/genética
Proteínas de Neoplasias/genética
Regiões Promotoras Genéticas
Pseudogenes
Sítio de Iniciação de Transcrição
Esclerose Tuberosa/diagnóstico
Esclerose Tuberosa/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GPI-Linked Proteins); 0 (Intercellular Signaling Peptides and Proteins); 0 (Neoplasm Proteins); 0 (Nuclear Pore Complex Proteins); 0 (Nup98 protein, human); 0 (TDGF1 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170831
[St] Status:MEDLINE
[do] DOI:10.1159/000479463


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[PMID]:28792952
[Au] Autor:Bissler JJ; Kingswood JC; Radzikowska E; Zonnenberg BA; Belousova E; Frost MD; Sauter M; Brakemeier S; de Vries PJ; Berkowitz N; Voi M; Peyrard S; Budde K
[Ad] Endereço:Department of Pediatric Nephrology, St. Jude Children's Research Hospital, Le Bonheur Children's Hospital, and the University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
[Ti] Título:Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study.
[So] Source:PLoS One;12(8):e0180939, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: We examined the long-term effects of everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. METHODS: Following favorable results from the double-blind core phase of EXIST-2 (NCT00790400), patients were allowed to receive open-label everolimus (extension phase). Patients initially randomly assigned to everolimus continued on the same dose; those who were receiving placebo crossed over to everolimus 10 mg/day. Dose modifications were based on tolerability. The primary end point was angiomyolipoma response rate, defined as a ≥50% reduction from baseline in the sum volume of target renal angiomyolipomas in the absence of new target angiomyolipomas, kidney volume increase of >20% from nadir, and angiomyolipoma-related bleeding grade ≥2. The key secondary end point was safety. RESULTS: Of the 112 patients who received ≥1 dose of everolimus, 58% (95% CI, 48.3% to 67.3%) achieved angiomyolipoma response. Almost all patients (97%) experienced reduction in renal lesion volumes at some point during the study period. Median duration of everolimus exposure was 46.9 months. Sixteen (14.3%) patients experienced angiomyolipoma progression at some point in the study. No angiomyolipoma-related bleeding or nephrectomies were reported. One patient on everolimus underwent embolization for worsening right flank pain. Subependymal giant cell astrocytoma lesion response was achieved in 48% of patients and skin lesion response in 68% of patients. The most common adverse events suspected to be treatment-related were stomatitis (42%), hypercholesterolemia (30.4%), acne (25.9%), aphthous stomatitis and nasopharyngitis (each 21.4%). Ten (8.9%) patients withdrew because of an adverse event. Renal function remained stable, and the frequency of emergent adverse events generally decreased over time. CONCLUSIONS: Everolimus treatment remained safe and effective over approximately 4 years. The overall risk/benefit assessment supports the use of everolimus as a viable treatment option for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00790400.
[Mh] Termos MeSH primário: Angiomiolipoma/tratamento farmacológico
Astrocitoma/tratamento farmacológico
Everolimo/uso terapêutico
Linfangioleiomiomatose/tratamento farmacológico
Esclerose Tuberosa/patologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antineoplásicos/uso terapêutico
Everolimo/efeitos adversos
Feminino
Volume Expiratório Forçado/efeitos dos fármacos
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
Resultado do Tratamento
Capacidade Vital/efeitos dos fármacos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antineoplastic Agents); 9HW64Q8G6G (Everolimus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180939



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