Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
1.
Am J Med Genet A ; 191(8): 2113-2131, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37377026

RESUMEN

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (>60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS-like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or "DTRs"). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype-phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population.


Asunto(s)
Síndrome de Cornelia de Lange , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Síndrome de Cornelia de Lange/diagnóstico , Síndrome de Cornelia de Lange/genética , Síndrome de Cornelia de Lange/patología , Factores de Transcripción/genética , Proteínas de Ciclo Celular/genética , Fenotipo , Mutación , Genómica , Estudios de Asociación Genética , Factores de Elongación Transcripcional/genética , Histona Desacetilasas/genética , Proteínas Represoras/genética
2.
Med Teach ; 31(8): e333-7, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19811195

RESUMEN

BACKGROUND: Despite dramatic increase in Internet-based CME activities, little is known about physician Internet CME preferences. AIMS: To identify the education format and resource preferences among registrants of a pediatric-focused CME website. METHODS: Preferences of physician registrants at PedsEducation.org between July 2000-November 2007 (n = 1388) were assessed via survey. A secondary analysis of respondent demographics vs. reported preferences was conducted. RESULTS: A total of 345 physicians participated (25% response rate). The majority (73%, n = 252) identified free CME as a highly important feature of an Internet CME resource; monthly case series was identified as the least important. Seventy-five percent of respondents (n = 260) identified practice guideline updates as a highly useful practice resource; practice feedback was identified as the least useful. Respondents with < or =10 years practice experience were more likely to identify case-based CME as highly useful to their daily practice (p < 0.001); respondents who spend > or = 90% working time on patient care were more likely to identify Internet CME as a highly useful CME format (p < 0.001). CONCLUSION: Internet CME preferences of PedsEducation.org registrants differ from those typically associated with knowledge gains and behavior changes. Demographic characteristics may influence these preferences.


Asunto(s)
Actitud del Personal de Salud , Educación Médica Continua/métodos , Pediatría/educación , Instrucción por Computador , Humanos , Internet
3.
JIMD Rep ; 46(1): 63-69, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31240156

RESUMEN

Succinyl-CoA synthetase or succinate-CoA ligase deficiency can result from biallelic mutations in SUCLG1 gene that encodes for the alpha subunit of the succinyl-CoA synthetase. Mutations in this gene were initially associated with fatal infantile lactic acidosis. We describe an individual with a novel biallelic pathogenic mutation in SUCLG1 with a less severe phenotype dominated by behavioral problems. The mutation was identified to be c.512A>G corresponding to a p.Asn171Ser change in the protein. The liquid chromatography tandem mass spectrometry-based enzyme activity assay on cultured fibroblasts revealed a markedly reduced activity of succinyl-CoA synthetase enzyme when both ATP and GTP were substrates, affecting both ADP-forming and GDP-forming functions of the enzyme.

5.
Nat Genet ; 44(11): 1249-54, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23023332

RESUMEN

Elevated transforming growth factor (TGF)-ß signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply diminished TGF-ß signaling. Taken together, these data have engendered controversy regarding the specific role of TGF-ß in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm. We identified causative variation in ten individuals with SGS in the proto-oncogene SKI, a known repressor of TGF-ß activity. Cultured dermal fibroblasts from affected individuals showed enhanced activation of TGF-ß signaling cascades and higher expression of TGF-ß-responsive genes relative to control cells. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in humans with SGS. These data support the conclusions that increased TGF-ß signaling is the mechanism underlying SGS and that high signaling contributes to multiple syndromic presentations of aortic aneurysm.


Asunto(s)
Aneurisma de la Aorta/genética , Aracnodactilia/genética , Craneosinostosis/genética , Proteínas de Unión al ADN , Síndrome de Marfan/genética , Proteínas Proto-Oncogénicas , Factor de Crecimiento Transformador beta , Animales , Aracnodactilia/metabolismo , Células Cultivadas , Craneosinostosis/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Fibroblastos , Humanos , Síndrome de Loeys-Dietz/genética , Síndrome de Marfan/metabolismo , Ratones , Mutación , Fenotipo , Fosforilación , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/genética , Pez Cebra
6.
Health Aff (Millwood) ; 26(2): 559-66, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17339686

RESUMEN

Newborn screening, which represents one of the major advances in child health of the past century, has been carried out in all fifty U.S. states since the 1970s. Newborn screening programs are state-run, and decisions are left to the individual states regarding the conditions to be screened for, the mechanism for confirmatory testing, follow-up care, and financing of the programs. Laboratory advances in tandem mass spectrometry make it possible to screen newborns for many rare inborn errors of metabolism. This raises many policy issues including screening's cost-effectiveness, ethics, quality, and oversight.


Asunto(s)
Enfermedades Genéticas Congénitas/epidemiología , Bienestar del Lactante , Tamizaje Neonatal/organización & administración , Análisis Costo-Beneficio , Femenino , Pruebas Genéticas/organización & administración , Política de Salud , Humanos , Recién Nacido , Masculino , Errores Innatos del Metabolismo/epidemiología , Formulación de Políticas , Prevención Primaria/organización & administración , Evaluación de Programas y Proyectos de Salud , Medición de Riesgo , Estados Unidos
7.
Curr Treat Options Neurol ; 5(4): 343-345, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12791201

RESUMEN

Despite the dramatic response of sick neonates with galactosemia to the withdrawal of galactose from the diet, over the long-term, complications, including learning disorders, verbal apraxia, and ataxia, often develop. It is clear that, although lifelong galactose restriction remains the basis of treatment for this disease, additional treatment methods are needed. The neurologist familiar with galactosemia can assist in diagnosis of neonates presenting with central nervous system symptoms. Familiarity with the long-term neurologic consequences of galactosemia can help the neurologist assist the family with prognostic information and to avoid unnecessary tests when complications occur.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA