Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations

Sahoo, Trilochan

doi:10.1136/jmg.2005.036913

Cited by 84 publications

(69 citation statements)

References 40 publications

(34 reference statements)

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“…Fluorescent in situ hybridization determines if a deletion has occurred. Chromosomal microarray can further refine the deletion size, which has been shown to correlate with severity of clinical features [8,11,12]. For those whom deletion is excluded by fluorescent in situ hybridization, DNA marker analysis of the proband's and parents' chromosome 15q11-q13 region will confirm or exclude UPD.…”

Section: Genetic Etiology and Diagnosismentioning

confidence: 99%

Angelman Syndrome

et al. 2015

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In this review we summarize the clinical and genetic aspects of Angelman syndrome (AS), its molecular and cellular underpinnings, and current treatment strategies. AS is a neurodevelopmental disorder characterized by severe cognitive disability, motor dysfunction, speech impairment, hyperactivity, and frequent seizures. AS is caused by disruption of the maternally expressed and paternally imprinted UBE3A, which encodes an E3 ubiquitin ligase. Four mechanisms that render the maternally inherited UBE3A nonfunctional are recognized, the most common of which is deletion of the maternal chromosomal region 15q11-q13. Remarkably, duplication of the same chromosomal region is one of the few characterized persistent genetic abnormalities associated with autistic spectrum disorder, occurring in >1-2 % of all cases of autism spectrum disorder. While the overall morphology of the brain and connectivity of neural projections appear largely normal in AS mouse models, major functional defects are detected at the level of context-dependent learning, as well as impaired maturation of hippocampal and neocortical circuits. While these findings demonstrate a crucial role for ubiquitin protein ligase E3A in synaptic development, the mechanisms by which deficiency of ubiquitin protein ligase E3A leads to AS pathophysiology in humans remain poorly understood. However, recent efforts have shown promise in restoring functions disrupted in AS mice, renewing hope that an effective treatment strategy can be found.Key Words Angelman syndrome . neurodevelopmental disorders . autism . ubiquitin ligase . Ube3a . Imprinting. Clinical OverviewIn 1965, the English physician Harry Angelman described 3 patients who presented with a stiff, jerky gait, absence of speech, excessive laughter, and seizures. The disorder that came to bear his name [Angelman syndrome (AS)] is now recognized to affect approximately 1 in 15,000 individuals and is characterized by motor dysfunction, severe intellectual disability, speech impairment, seizures, hyperactivity, and autism spectrum disorder (ASD) as a common comorbidity [1].Developmental delay in individuals with AS is usually observed within the first year of life. Though most individuals lack speech entirely, some who are mildly affected can acquire a few words. Receptive language is less impaired. Seizures occur in >80 % of patients, and onset is usually before the age of 3 years. Movement disorders include tremors, jerkiness, and ataxia. The characteristic behaviors of AS include mouthing of objects, happy demeanor with easily provoked laughter, attraction to water, hyperactivity, short attention span, and decreased sleeping (see recent reviews for more detailed description of the clinical phenotype [2][3][4]). These features of AS can be seen in other neurodevelopmental disorders, leading to a broad differential diagnosis [5], which has recently been reviewed (Table 1) [6]. Overlapping clinical features may indicate common neurophysiological pathways,

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Section: Genetic Etiology and Diagnosismentioning

confidence: 99%

Angelman Syndrome

et al. 2015

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“…Los individuos con mutaciones en el UBE3A manifiestan un fenotipo de gravedad intermedia. 9 El manejo debe enfocarse en las condiciones que generan más impacto en la calidad de vida y producen mayor deterioro neurológico. El control inadecuado de la epilepsia, los trastornos de sueño y comorbilidades psiquiátricas puede empeorar su condición.…”

Section: Casos Clínicosunclassified

Del fenotipo neuropsiquiátrico al cuidado clínico del síndrome de Angelman: descripción de siete casos

2017

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RESUMENEl síndrome de Angelman es un trastorno neurogenético debido a la falta o reducción en la expresión del gen UBE3A en el cromosoma 15, el cual codifica la proteína ubiquitina ligasa E3A, que tiene un papel integral en el desarrollo sináptico y la plasticidad neuronal. Se manifiesta por retraso en el neurodesarrollo o discapacidad intelectual, comportamiento característico y epilepsia. Se describen las características clínicas de siete pacientes con deleción del cromosoma 15q11-13 y su manejo integral. Por la expectativa de vida, es importante conocer y manejar las comorbilidades de forma interdisciplinaria para lograr mejorar la calidad de vida de los afectados. Se realiza una revisión de la literatura sobre la aproximación integral al diagnóstico y cuidado clínico a largo plazo de los pacientes con síndrome de Angelman. Palabras clave: síndrome de Angelman, cromosoma 15q11-13, UBE3A, niño, impronta molecular. ABSTRACTAngelman syndrome is a neurogenetic disorder caused by a lack or reduction of expression of UBE3A located within chromosome 15, which codes for ubiquitin protein ligase E3A, which has a key role in synaptic development and neural plasticity. Its main features are developmental delay/intellectual disability, lack of speech, a characteristic behavioural profile, and epilepsy. We describe clinical features and management of seven cases with 15q11-13 deletion. Due to their life expectancy, knowing and managing its comorbidities is crucial to improve their quality of life. We review the diagnosis and long-term clinical care of patients with Angelman syndrome.

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“…Such an increased 'set-level' of demands imposed on mothers might be expected to lead to insecure forms of attachment, unless the demands are met, whereupon social-emotional development should proceed as normally as possible under the circumstances of severe intellectual disability that characterize this syndrome. A high prevalence of autistic traits in Angelman syndrome (Sahoo et al 2006;Bonati et al 2007;Jedele 2007) has also been interpreted in the context of selectively-reduced social-brain development and high demands imposed on the mother in the context of paternal imprinted-gene bias (Brown and Consedine 2004;Isles et al 2006;Crespi and Badcock 2008).…”

Section: Angelman Syndromementioning

confidence: 99%

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

Crespi

2011

Brain, Behavior and Epigenetics

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I describe and evaluate the hypothesis that effects from parent-offspring conflict and genomic imprinting on human neurodevelopment and behavior are central to evolved systems of mother-child attachment. The psychological constructs of Bowlby's attachment theory provide phenomenological descriptions of how attachment orchestrates affective-cognitive development, and patterns of imprinted gene expression and co-expression provide evidence of epigenetic and evolutionary underpinnings to human growth and neurodevelopment. Social-environmental perturbations to the development of normally-secure attachment, and alterations to evolved systems of parent-offspring conflict and imprinted-gene effects, are expected to lead to specific forms of maladaptation, manifest in psychiatric conditions affecting social-brain development. In particular, under-development of the social brain in autism may be mediated in part by mechanisms that lead to physically enhanced yet psychologically under-developed attachment to the mother, and affective-psychotic conditions, such as schizophrenia and depression, may be mediated in part by forms of insecure attachment and by increased relative effects of the maternal brain, both directly from mothers and via imprinted-gene effects in offspring. These hypotheses are concordant with findings from epidemiology, attachment theory, psychiatry, and genetic and epigenetic analyses of risk factors for autism and affective-psychotic conditions, they make novel predictions for explaining the causes of psychosis in Prader-Willi syndrome and idiopathic schizophrenia, and they suggest avenues for therapeutic interventions based on normalizing alterations to epigenetic networks and targeting public-health interventions towards reduction of perturbations to the development of secure attachment in early childhood and individuation during adolescence.

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Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations

Cited by 84 publications

References 40 publications

Angelman Syndrome

Angelman Syndrome

Del fenotipo neuropsiquiátrico al cuidado clínico del síndrome de Angelman: descripción de siete casos

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

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