Detection of a novel familial deletion of four genes between BP1 and BP2 of the Prader-Willi/Angelman syndrome critical region by oligo-array CGH in a child with neurological disorder and speech impairment

2007 ◽  
Vol 116 (1-2) ◽  
pp. 135-140 ◽  
Author(s):  
S.K. Murthy ◽  
A.O.H. Nygren ◽  
H.M. El Shakankiry ◽  
J.P. Schouten ◽  
A.I. Al Khayat ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Critical Region ◽  
Neurological Disorder ◽  
Array Cgh ◽  
Speech Impairment ◽  
Oligo Array

Angelman Syndrome due to a Maternally Inherited Intragenic Deletion Encompassing Exons 7 and 8 of the UBE3A Gene

2017 ◽  
Vol 152 (3) ◽  
pp. 132-136
Author(s):  
Athina Ververi ◽  
Lily Islam ◽  
Beverley Bewes ◽  
Louise Busby ◽  
Caroline Sullivan ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Angelman Syndrome ◽  
Array Cgh ◽  
De Novo ◽  
Uniparental Disomy ◽  
Genetic Mechanism ◽  
Paternal Allele ◽  
Speech Impairment ◽  
Intragenic Deletion ◽  
Ube3a Gene

Angelman syndrome (AS) is characterised by developmental delay, lack of speech, seizures, a characteristic behavioural profile with a happy demeanour, microcephaly, and ataxia. More than two-thirds of cases are due to an approximately 5-Mb interstitial deletion of the imprinted region 15q11.2q13, which is usually de novo. The rest are associated with point mutations in the UBE3A gene, imprinting defects, and paternal uniparental disomy. Small intragenic UBE3A deletions have rarely been described. They are usually maternally inherited, increasing the recurrence risk to 50%, and may be missed by conventional testing (methylation studies and UBE3A gene sequencing). We describe a boy with AS due to an 11.7-kb intragenic deletion. The deletion was identified by array-CGH and was subsequently detected in his affected first cousin and unaffected maternal grandfather, mother, and aunt, confirming the silencing of the paternal allele. The patient had developmental delay, speech impairment, a happy demeanour, microcephaly, and an abnormal EEG, but no seizures by the age of 4 years. Delineation of the underlying genetic mechanism is of utmost importance for reasons of genetic counselling, as well as appropriate management and prognosis. Alternative techniques, such as array-CGH and MLPA, are necessary when conventional testing for AS has failed to identify the underlying genetic mechanism.

Partial hexasomy for the Prader-Willi-Angelman syndrome critical region due to a maternally inherited large supernumerary marker chromosome

2010 ◽  
Vol 152A (8) ◽  
pp. 2034-2038 ◽  
Author(s):  
Nicole L. Hoppman-Chaney ◽  
D. Brian Dawson ◽  
Lai Nguyen ◽  
Sunanda Sengupta ◽  
Kara Reynolds ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Critical Region ◽  
Marker Chromosome

scholarly journals Angelman Syndrome: An Autism Spectrum Disorder

2018 ◽  
Vol 6 (2) ◽  
pp. 56-60
Author(s):  
Andrew J. Kennedy ◽  
Jeffrey O. Henderson
Keyword(s):  
Angelman Syndrome ◽  
Motor Development ◽  
Neurodevelopmental Disorders ◽  
Muscle Tension ◽  
Autism Spectrum ◽  
Speech Impairment ◽  
Social Lives ◽  
Genetic Abnormalities ◽  
Ube3a Gene ◽  
Genetic Mechanisms

Neurodevelopmental disorders limit the mental, physical, and social lives of affected individuals and their families. These disorders are often related to genetic abnormalities having a distinct chromosomal location. The abnormalities can cause incorrect proteins to be formed or biochemical pathways to be blocked, predominately affecting brain development, but also having pleiotropic effects. Research into defining and correcting these genetic abnormalities is important to help distinguish between unique neurodevelopmental disorders so that proper clinical interventions are available for affected individuals. In the following review, Angelman syndrome, which results from UBE3A gene function being lost at maternal chromosome  15q11.2-q13, will be discussed. Angelman patients suffer from the defining characteristics of speech impairment, uncontrolled laughing and smiling, motor development issues, muscle tension, and possible ataxia. The genetic mechanisms of the disorder as well as possible therapies will be discussed, with future areas of research into genetic therapies to treat Angelman syndrome also put forth. Research into Angelman syndrome can provide an avenue for a clearer understanding of other neurodevelopmental disorders.

scholarly journals A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Giorgia Mandrile ◽  
Eleonora Di Gregorio ◽  
Alessandro Calcia ◽  
Alessandro Brussino ◽  
Enrico Grosso ◽  
...  
Keyword(s):  
Clinical Features ◽  
Critical Region ◽  
Array Cgh ◽  
De Novo ◽  
Genetic Disorder ◽  
Phenotypic Expression ◽  
Microdeletion Syndrome ◽  
Complex Rearrangement

A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely,KATNAL1, LINC00426, andHMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified ade novomicrodeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development.

Angelman Syndrome

2013 ◽  
Author(s):  
Edwin J. Weeber
Keyword(s):  
Developmental Delay ◽  
Angelman Syndrome ◽  
Neurological Disorder ◽  
Motor Coordination ◽  
Clinical Presentation ◽  
Sleep Disruption ◽  
Behavioral Difficulties ◽  
Symptom Complex ◽  
Degrees Of Severity

Angelman syndrome (AS) is a devastating neurological disorder with a symptom complex that includes but is not limited to severe developmental delay, profound cognitive disruption, motor coordination defects, increased propensity for seizure with a characteristic abnormal electroencephalogram, sleep disruption, behavioral difficulties, a lack of speech, and an overall happy demeanor. Although the disorder was first described in 1965 by British pediatrician Dr. Harry Angelman, because AS is clinically characterized by a wide constellation of symptoms with varying degrees of severity, it is not readily diagnosed by clinical presentation alone and misdiagnosis has commonly occurred.

scholarly journals The Angelman Syndrome-Associated Protein, E6-AP, Is a Coactivator for the Nuclear Hormone Receptor Superfamily

1999 ◽  
Vol 19 (2) ◽  
pp. 1182-1189 ◽  
Author(s):  
Zafar Nawaz ◽  
David M. Lonard ◽  
Carolyn L. Smith ◽  
Efrat Lev-Lehman ◽  
Sophia Y. Tsai ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Degradation Pathway ◽  
Nuclear Hormone Receptor ◽  
Dependent Manner ◽  
Speech Impairment ◽  
Ubiquitin Protein Ligase ◽  
Independent Functions ◽  
Ligase Function

ABSTRACT In this study, we found that the E6-associated protein (E6-AP/UBE3A) directly interacts with and coactivates the transcriptional activity of the human progesterone receptor (PR) in a hormone-dependent manner. E6-AP also coactivates the hormone-dependent transcriptional activities of the other members of the nuclear hormone receptor superfamily. Previously, it was shown that E6-AP serves the role of a ubiquitin-protein ligase (E3) in the presence of the E6 protein from human papillomavirus types 16 and 18. Our data show that the ubiquitin-protein ligase function of E6-AP is dispensable for its ability to coactivate nuclear hormone receptors, showing that E6-AP possesses two separable independent functions, as both a coactivator and a ubiquitin-protein ligase. Disruption of the maternal copy of E6-AP is correlated with Angelman syndrome (AS), a genetic neurological disorder characterized by severe mental retardation, seizures, speech impairment, and other symptoms. However, the exact mechanism by which the defective E6-AP gene causes AS remains unknown. To correlate the E6-AP coactivator function and ubiquitin-protein ligase functions with the AS phenotype, we expressed mutant forms of E6-AP isolated from AS patients and assessed the ability of each of these mutant proteins to coactivate PR or provide ubiquitin-protein ligase activity. This analysis revealed that in the majority of the AS patients examined, the ubiquitin-protein ligase function of E6-AP was defective whereas the coactivator function was intact. This finding suggests that the AS phenotype results from a defect in the ubiquitin-proteosome protein degradation pathway.

scholarly journals Electrophysiological Characterization of Regular and Burst Firing Pyramidal Neurons of the Dorsal Subiculum in an Angelman Syndrome Mouse Model

2021 ◽  
Vol 15 ◽  
Author(s):  
Prudhvi Raj Rayi ◽  
Hanoch Kaphzan
Keyword(s):  
Mouse Model ◽  
Angelman Syndrome ◽  
Pyramidal Neurons ◽  
Neuropsychiatric Disorders ◽  
Brain Regions ◽  
Membrane Properties ◽  
Speech Impairment ◽  
Behavioral Deficits ◽  
Single Action ◽  
Hippocampal Ca1

Angelman syndrome (AS) is a debilitating neurogenetic disorder characterized by severe developmental delay, speech impairment, gait ataxia, sleep disturbances, epilepsy, and a unique behavioral phenotype. AS is caused by a microdeletion or mutation in the maternal 15q11-q13 chromosome region containing UBE3A gene. The hippocampus is one of the important brain regions affected in AS mice leading to substantial hippocampal-dependent cognitive and behavioral deficits. Recent studies have suggested an abnormal increase in the α1-Na/K-ATPase (α1-NaKA) in AS mice as the precipitating factor leading to the hippocampal deficits. A subsequent study showed that the hippocampal-dependent behavioral deficits occur as a result of altered calcium (Ca+2) dynamics in the CA1 pyramidal neurons (PNs) caused by the elevated α1-NaKA expression levels in the AS mice. Nonetheless, a causal link between hippocampal deficits and major behavioral phenotypes in AS is still obscure. Subiculum, a region adjacent to the hippocampal CA1 is the major output source of the hippocampus and plays an important role in the transfer of information from the CA1 region to the cortical areas. However, in spite of the robust hippocampal deficits and several known electrophysiological alterations in multiple brain regions in AS mice, the neuronal properties of the subicular neurons were never investigated in these mice. Additionally, subicular function is also implied in many neuropsychiatric disorders such as autism, schizophrenia, Alzheimer’s disease, and epilepsy that share some common features with AS. Therefore, given the importance of the subiculum in these neuropsychiatric disorders and the altered electrophysiological properties of the hippocampal CA1 PNs projecting to the subiculum, we sought to examine the subicular PNs. We performed whole-cell recordings from dorsal subiculum of both WT and AS mice and found three distinct populations of PNs based on their ability to fire bursts or single action potentials following somatic current injection: strong bursting, weak bursting, and regular firing neurons. We found no overall differences in the distribution of these different subicular PN populations among AS and WT controls. However, the different cell types showed distinct alterations in their intrinsic membrane properties. Further, none of these populations were altered in their excitatory synaptic properties. Altogether, our study characterized the different subtypes of PNs in the subicular region of an AS mouse model.

scholarly journals Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH: molecular characterization and genotype–phenotype correlations

2007 ◽  
Vol 15 (9) ◽  
pp. 943-949 ◽  
Author(s):  
Trilochan Sahoo ◽  
Carlos A Bacino ◽  
Jennifer R German ◽  
Chad A Shaw ◽  
Lynne M Bird ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Angelman Syndrome ◽  
Array Cgh
Sign in / Sign up

Export Citation Format

Share Document