Pamela Watson, Graeme Black, Simon Ramsden, Margaret Barrow, Maurice Super, Bronwyn Kerr, Jill Clayton-Smith

J Med Genet 2001 38: 224-228
doi: 10.1136/jmg.38.4.224

Angelman syndrome (AS) is a neurodevelopmental disorder characterised by severe mental retardation, absent speech, ataxia, sociable affect, and dysmorphic facial features. Eighty five percent of patients with AS have an identifiable genetic abnormality of chromosome 15q11-13. Mutations within the X linkedMECP2 gene have been identified in patients with Rett syndrome (RTT), a neurodevelopmental disorder which affects females almost exclusively and which shares phenotypic overlap with AS. RTT is usually associated with normal development in infancy followed by loss of acquired skills and evolution of characteristic hand wringing movements and episodes of hyperventilation.

A panel of 25 female and 22 male patients with a clinical diagnosis of AS and no molecular abnormality of 15q11-13 were screened for MECP2 mutations and these were identified in four females and one male. Following the diagnosis, it was possible to elicit a history of regression in three of these patients, who by then were showing features suggestive of Rett syndrome. In the remaining two subjects the clinical phenotype was still considered to be Angelman-like.

These findings illustrate the phenotypic overlap between the two conditions and suggest that screening forMECP2 mutations should be considered in AS patients without a demonstrable molecular or cytogenetic abnormality of 15q11-13. Since MECP2 mutations almost always occur de novo, their identification will substantially affect genetic counselling for the families concerned.

 

The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology.

Scott V. Dindot, Barbara A. Antalffy, Meenakshi B. Bhattacharjee and Arthur L. Beaudet

Hum Mol Genet. 2007 Oct 16

Assisted reproductive therapies and imprinting disorders - preliminary British survey

James S Sutcliffe et al

Human Reproduction Vol.21, No.4 pp. 1009-1011, 2006

Autism and Maternally Derived Aberrations of Chromosome 15

Richard J. Schroer et al.

American Journal of Medical Genetics
76: 327-336 (1998)

Autism spectrum disorders in Prader-Willi and Angelman syndromes: a systematic review

Veltman, Marijcke et al

Psychiatric Genetics
2005. 15: 243254

Document linked to :http://www.ncbi.nlm.nih.gov/entrez/query.fcgicmd=Retrieve&db=PubMed&list_uids=2006012&dopt=Abstract Link created on :Tue, 2007-Feb-20 23:26

Document linked to :http://www.ncbi.nlm.nih.gov/entrez/query.fcgicmd=Retrieve&db=PubMed&list_uids=2006012&dopt=Abstract Link created on :Tue, 2007-Feb-20 23:26

 

Behavior and neuropsychiatric manifestations in Angelman syndrome.

Pelc K, Cheron G, Dan B.

Neuropsychiatr Dis Treat. 2008 Jun;4(3):577-84

Behavioural flexibility in individuals with Angelman syndrome, Down syndrome, non-specific intellectual disability and Autism spectrum disorder R. Didden,J. Sigafoos,V. A. Green, H. Korzilius,1 C. Mouws, G. E. Lancioni, M. F. O?Reilly,L. M. G. Curfs Journal of Intellectual Disability Research doi: 10.1111/j.1365-2788.2008.01055

 

Characterisation of interstitial duplications and triplications of chromosome 15q11-q13

Siân E. Roberts et al

Human Genetic
(2002) 110 :227-234

Characterisation of interstitial duplications and triplications of chromosome 15q11-q13

Siân E. Roberts et al

Human Genetics
110 :227-234

Control elements within the PWS/AS imprinting box and their function in the imprinting process

Boris Kantor et al

Human Molecular Genetics
2004, Vol. 13, No. 7

Detailed analysis of 15q11-q14 sequence corrects errors and gaps in
the public access sequence to fully reveal large segmental
duplications at breakpoints for Prader-Willi, Angelman, and inv
dup(15) syndromes

Andrew J Makoff and Rachel H Flomen

8th June 2007

Diagnostic Testing for Prader-Willi and Angelman Syndromes: Report of the ASHG/ACMG Test and Technology Transfer Committee

ASHG/ACMG Report

American Society of Human Genetics/American College of Medical Genetics Test and Technology Transfer Committee

Am. J. Hum. Genet. 58:1085---1088, 1996

Angelman syndrome (AS) is caused by reduced or absent expressionof the maternally inherited ubiquitin protein ligase 3A gene(UBE3A), which maps to chromosome 15q11?q13. UBE3A issubject to genomic imprinting in neurons in most regions of thebrain. Expression of UBE3A from the maternal chromosome isessential to prevent AS, because the paternally inherited gene isnot expressed, probably mediated by antisense UBE3A RNA. Wehypothesized that increasing methylation might reduce expressionof the antisense UBE3A RNA, thereby increasing UBE3Aexpression from the paternal gene and ameliorating the clinicalphenotype. We conducted a trial using two dietary supplements,betaine and folic acid to promote global levels of methylationand attempt to activate the paternally inherited UBE3A gene.We performed a number of investigations at regular intervalsincluding general clinical and developmental evaluations, biochemicaldeterminations on blood and urine, and electroencephalographicstudies.Wereport herein the data on 48 children withAS who were enrolled in a double-blind placebo-controlledprotocol using betaine and folic acid for 1 year. There were nostatistically significant changes between treated and untreatedchildren; however, in a small subset of patients we observed somepositive trends.

Peters SU, Bird LM, Kimonis V, Glaze DG,Shinawi LM, Bichell TJ, Barbieri-Welge R,Nespeca M, Anselm I, Waisbren S, Sanborn E,Sun Q, O?Brien WE, Beaudet AL, Bacino CA.2010.

Double-blind therapeutic trial inAngelman syndrome using betaine and folicacid.

Am J Med Genet Part A 152A:1994?2001.

The Drosophila homologue of the Angelman syndrome ubiquitin
ligase regulates the formation of terminal dendritic branches

Yubing Lu, Fay Wang, Yan Li, Jacob Ferris, Jin-A Lee, Fen-Biao Gao

Hum Mol Genet 2008
This article also has been translated into non scientific language in the section Nina's Journal club

Chris Oliver, Louisa Demetriades, and Scott HallUniversity of BirminghamAbstractAngelman syndrome is a neurogenetic disorder associated with unique behaviors and characteristics,including an unusually happy expression, inability to speak, ataxia, mental retardation,and abnormal EEG. Previous research has suggested that smiling and laughingbehaviors in Angelman syndrome are inappropriate, excessive, and dissociated from contextualevents. In the present study, the variability of smiling and laughing behaviors of 3individuals with Angelman syndrome was examined across typical social contexts. Resultsindicate that laughing and smiling increased during social situations and occurred at lowlevels during non-social situations. The behaviors, therefore, did not occur totally inappropriately,as has been suggested. The findings illustrate the need to divert attention tothe examination of environmental influences on purported phenotypic behavior in geneticsyndromes.

Efficacy of Anti-Epileptic Medications in Angelman Syndrome

T. J. Bichell, V. Kimonis, E. Sanborn, C. Bacino, A. Beaudet, L. Bird, M. Nespeca

Presentation held by Mrs. Terry Bichell at the 2007 ASF Biennial Conference (July 24 - July 28) at the Hyatt Regency St. Louis, United States of America

Electroclinical characteristics of seizures-comparing Prader-Willi syndrome with Angelman syndrome

Wang, Pen-Jung et al

Brain & Development
27 (2005) 101-107

Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3

Rodney C. Samaco et al

Human Molecular Genetics
2005, Vol. 14, No. 4