Browsing by Author "Nunes, L"
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- Birt-Hogg-Dubé SyndromePublication . Lencastre, A; Ponte, P; Apetato, M; Nunes, L; Lestre, SA 45-year-old woman with a history of renal carcinoma was observed for facial, cervical and truncal flesh-colored papules. Relatives had similar skin findings and a brother had repeated episodes of pneumothorax. The computerized tomography scan revealed multiple cysts on both lungs. A skin biopsy revealed a perifollicular fibroma. The clinical diagnosis of Birt-Hogg-Dubé syndrome (BHDS) was corroborated by identification of a novel frameshift c.573delGAinsT (p.G191fsX31) mutation in heterozygosity on exon 6 of the folliculin gene. The presence of multiple and typical benign hair follicle tumors highlights the role of the dermatologist in the diagnosis of this rare genodermatosis that is associated with an increased risk of renal cell cancer and pulmonary cysts, warranting personal and familial follow-up and counseling.
- Genetic Screening of LCA in Belgium: Predominance of CEP290 and Identification of Potential Modifier Alleles in AHI1 of CEP290-Related PhenotypesPublication . Coppieters, F; Casteels, I; Meire, F; De Jaegere, S; Hooghe, S; van Regemorter, N; Van Esch, H; Matuleviciene, A; Nunes, L; Meersschaut, V; Walraedt, S; Standaert, L; Coucke, P; Hoeben, H; Kroes, H; Vande Walle, J; de Ravel, T; Leroy, B; De Baere, ELeber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease.
- Macrossomia, Hipersomnia e Alteração do Controlo da Temperatura: Disfunção Hipotalâmica de Causa DesconhecidaPublication . Jacinto, S; Silva, R; Lopes, P; Nunes, L; Romão, G; Calado, E
- Mosaic Trisomy 18 in a Five-Month-Old Infant - Case ReportPublication . Fitas, AL; Paiva, M; Cordeiro, AI; Nunes, L; Cordeiro Ferreira, GIndividuals with mosaic trisomy 18, only approximately 5% of all trisomy 18 cases, carry both a trisomy 18 and an euploid cell line. Their clinical findings are highly variable, from the absence of dysmorphic features to the complete trisomy 18 syndrome. A five month old daughter of a 38-year-old mother, with vomiting and feeding problems, was referred to our department. She was undernourished and had axial hypotony and developmental delay, an irregular pattern of hypopigmentation on the right side of the abdomen, and moderate sagittal body asymmetry with left-side muscular hemihypotrophy.Mild craniofacial dysmorphy included dolichocephaly, frontal bossing, prominent occiput, long downslanting palpebral fissures, hypertelorism, and retrognathia. A complex heart defect with atrial and ventricular septal defects, pulmonary artery stenosis, and bicuspid aortic valve was identified. Cytogenetic analysis revealedmosaic trisomy 18with trisomy in 90%of peripheral lymphocytes and 17%of skin fibroblasts.This case adds to our knowledge of the phenotypic spectrum and the natural history of mosaic trisomy 18 by adding a dysmorphic feature and a cardiac abnormality that, to the best of our knowledge, had not been previously described.
- Mutations in CTC1, Encoding Conserved Telomere Maintenance Component 1, Cause Coats PlusPublication . Anderson, B; Kasher, P; Mayer, J; Szynkiewicz, M; Jenkinson, E; Bhaskar, S; Urquhart, J; Daly, S; Dickerson, J; O'Sullivan, J; Leibundgut, E; Muter, J; Abdel-Salem, G; Babul-Hirji, R; Baxter, P; Berger, A; Bonafé, L; Brunstom-Hernandez, J; Buckard, J; Chitayat, D; Chong, W; Cordelli, D; Ferreira, P; Fluss, J; Forrest, E; Franzoni, E; Garone, C; Hammans, S; Houge, G; Hughes, I; Jacquemont, S; Jeannet, P; Jefferson, R; Kumar, R; Kutschke, G; Lundberg, S; Lourenço, C; Mehta, R; Naidu, S; Nischal, K; Nunes, L; Ounap, K; Philippart, M; Prabhakar, P; Risen, S; Schiffmann, R; Soh, C; Stephenson, J; Stewart, H; Stone, J; Tolmie, J; van der Knaap, M; Vieira, JP; Vilain, C; Wakeling, E; Wermenbol, V; Whitney, A; Lovell, S; Meyer, S; Livingston, J; Baerlocher, G; Black, G; Rice, G; Crow, YCoats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
- O Papel do Rastreio Auditivo Neonatal na Reabilitação Auditiva InfantilPublication . Araújo-Martins, J; Correia, I; Ferreira, R; Santos, PB; Gonçalves, R; Almeida, S; Nunes, L; Monteiro, LObjectivos: Determinar a influência da implementação do rastreio auditivo neonatal universal na referenciação de crianças com hipoacúsia a uma consulta de reabilitação auditiva. Métodos: Contexto – consulta de reabilitação auditiva num centro de referenciação terciário em Lisboa; Desenho do estudo – estudo de coorte retrospectivo baseado nos dados de processos clínicos de crianças com surdez. População – todos os processos de crianças nascidas a partir de 1998 (437 no total) foram analisados, resultando na selecção de 322 crianças que cumpriam os critérios de inclusão. Resultados: A idade média de referenciação à consulta tem vindo a diminuir de 55 meses (1998-2000) para 12 meses (2007-2009). Em 3/4 dos doentes o motivo de referenciação é hipoacúsia ou alterações nos programas de rastreio auditivo neonatal. Conclusão: O rastreio auditivo neonatal tem permitido iniciara reabilitação auditiva de crianças com hipoacúsia mais cedo. É importante manter este programa a funcionar para garantir a reabilitação precoce de crianças com perda auditiva.
- A Síndrome de Smith-Lemli-Opitz: Características Fenotípicas e Genotípicas dos Doentes PortuguesesPublication . Cardoso, ML; Bandeira, A; Lopes, A; Rodrigues, M; Venâncio, M; Sales Marques, J; Janeiro, P; Ferreira, I; Quelhas, D; Sequeira, S; Soares, G; Lourenço, T; Rodrigues, R; Gaspar, A; Nunes, L; Marques, F; Martins, EA síndrome de Smith-Lemli-Opitz (SLOS) é uma síndrome polimalformativa de transmissão autossómica recessiva causada por um défice metabólico da biossíntese do colesterol, que se caracteriza por dismorfias craniofaciais, anomalias congénitas de vários órgãos (salientando-se as do esqueleto e do aparelho urogenital), restrição de crescimento intra-uterino (RCIU), alterações comportamentais e atraso mental. É causada por mutações no gene DHCR7, que codifica para a enzima 7-dehidrocolesterol reductase, responsável pelo último passo da via metabólica da síntese do colesterol. A SLOS caracteriza-se por níveis diminuídos de colesterol e concentrações altas do seu precursor, 7-dehidrocolesterol, no sangue e tecidos. Procedeu-se a uma análise comparativa dos fenótipo e genótipo de quinze casos de SLOS de origem portuguesa, e são tecidas considerações quanto às dificuldades e limitações inerentes ao diagnóstico, e ao facto de esta doença hereditária do metabolismo dever ser considerada no diagnóstico diferencial das situações de (i) hipocolesterolémia, (ii) RCIU e (iii) síndromes polimalformativas,(especialmente quando crianças com atraso de crescimento apresentam simultaneamente sindactilia do segundo e terceiro dedos do pé e microcefalia e/ou narinas antevertidas entre outras anomalias).
- Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With DiabetesPublication . Van Belle, E; Cosenza, A; Bravo Baptista, S; Vincent, F; Henderson, J; Santos, L; Ramos, R; Pouillot, C; Calé, R; Cuisset, T; Jorge, E; Teiger, E; Machado, C; Belle, L; Costa, M; Barreau, D; Oliveira, E; Hanssen, M; Costa, J; Besnard, C; Nunes, L; Dallongeville, J; Sideris, G; Bretelle, C; Fonseca, N; Lhoest, N; Guardado, J; Silva, B; Sousa, MJ; Barnay, P; Silva, JC; Leborgne, L; Rodrigues, A; Porouchani, S; Seca, L; Fernandes, R; Dupouy, P; Raposo, LImportance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, setting, and participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main outcomes and measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.