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1.
Am J Med Genet A ; 185(1): 168-181, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33108066

RESUMO

Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe the evolution of the clinical phenotypes of AS in adulthood, using clinical data from 95 individuals (mean age 31.6 years, median 29.0 years, range 18-83 years), with genetically confirmed AS. Data was collected through physical examination and inspection of medical records, combined with questionnaires and interviews. Adults with AS experience substantial debilitating health problems. Constipation, reflux, visual problems, scoliosis, behavioral and sleeping problems occurred frequently and require appropriate attention. Epilepsy was reported in 57% of adults, negatively affecting the level of functioning. Non-convulsive status epilepticus was not observed in the adults, however some individuals developed prolonged episodes of rhythmic shaking while awake. A decline in mobility was noted in the majority of adults. A minority of adults with AS showed microcephaly. Taken together, this first phenotypic study of adults with AS to include in person interviews with care-givers and physical examination of patients, including the eldest adult reported to date, provides important insight in the development of the syndrome into adulthood. This knowledge is required to improve care for adult individuals with AS and to evaluate future therapies for this group.


Assuntos
Síndrome de Angelman/diagnóstico , Síndrome de Angelman/epidemiologia , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome de Angelman/complicações , Síndrome de Angelman/fisiopatologia , Epilepsia/complicações , Epilepsia/fisiopatologia , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
2.
Mol Genet Genomic Med ; 8(11): e1481, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889787

RESUMO

BACKGROUND: Loss of functional UBE3A, an E3 protein ubiquitin ligase, causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, speech impairment, epilepsy, movement or balance disorder, and a characteristic behavioral pattern. We identified a novel UBE3A sequence variant in a large family with eight affected individuals, who did not meet the clinical AS criteria. METHODS: Detailed clinical examination and genetic analysis was performed to establish the phenotypic diversity and the genetic cause. The function of the mutant UBE3A protein was assessed with respect to its subcellular localization, stability, and E3 ubiquitin ligase activity. RESULTS: All eight affected individuals showed the presence of a novel maternally inherited UBE3A sequence variant (NM_130838.4(UBE3A):c.1018-1020del, p.(Asn340del), which is in line with a genetic AS diagnosis. Although they presented with moderate to severe intellectual disability, the phenotype did not match the clinical criteria for AS. In line with this, functional analysis of the UBE3A p.Asn340del mutant protein revealed no major deficits in UBE3A protein localization, stability, or E3 ubiquitin ligase activity. CONCLUSION: The p.(Asn340del) mutant protein behaves distinctly different from previously described AS-linked missense mutations in UBE3A, and causes a phenotype that is markedly different from AS. This study further extends the range of phenotypes that are associated with UBE3A loss, duplication, or mutation.


Assuntos
Síndrome de Angelman/genética , Deficiências do Desenvolvimento/genética , Deleção de Genes , Fenótipo , Ubiquitina-Proteína Ligases/genética , Adulto , Síndrome de Angelman/diagnóstico , Animais , Deficiências do Desenvolvimento/diagnóstico , Diagnóstico Diferencial , Estabilidade Enzimática , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Linhagem , Transporte Proteico , Ubiquitina-Proteína Ligases/metabolismo
3.
Ned Tijdschr Geneeskd ; 155: A2303, 2011.
Artigo em Holandês | MEDLINE | ID: mdl-21649944

RESUMO

OBJECTIVE: To investigate which ethical considerations play a role in the assessment of absenteeism due to sickness and of disability, and how these are dealt with. DESIGN: Qualitative, exploratory study. METHOD: We conducted interviews with 32 individual professional practitioners: 8 occupational health physicians, 8 insurance company physicians, 8 general practitioners, and 8 psychologists, with the aid of a semi-structured questionnaire. During the interview we differentiated between 4 clusters of questions referring to the ethical, legal, interdisciplinary, and professional context, respectively. The study revealed only the spectrum of ethical considerations that played a role, and not the representativeness. For this reason the results did not allow for quantitative conclusions. RESULTS: Differences in the manner of thinking and behaving between health-care providers stem from differences in ethical considerations and in background beliefs. These differences hinder effective cooperation within the occupational health sector. CONCLUSION: To improve professional performance and to achieve more responsible decision-making those involved need to be aware of their ethical considerations and background beliefs and to make them explicit, possibly with the aid of a checklist.


Assuntos
Absenteísmo , Tomada de Decisões , Saúde Ocupacional/estatística & dados numéricos , Equipe de Assistência ao Paciente/ética , Licença Médica , Avaliação da Deficiência , Humanos , Países Baixos , Saúde Ocupacional/legislação & jurisprudência , Equipe de Assistência ao Paciente/normas , Papel Profissional , Responsabilidade Social
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