Angelman syndrome phenotype associated with mutations inMECP2, a gene encoding a methyl CpG binding protein
- Pamela Watsona,
- Graeme Blacka,b,
- Simon Ramsdena,
- Margaret Barrowc,
- Maurice Superd,
- Bronwyn Kerrd,
- Jill Clayton-Smitha
- aRegional Genetic Service, St Mary's Hospital, Hathersage Road, Manchester M13 OJH, UK, bUniversity Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester M13 9WH, UK, cClinical Genetics Service, Leicester Royal Infirmary, Leicester LE1 5WW, UK, dDepartment of Paediatric Genetics, Royal Manchester Children's Hospital, Pendlebury, Manchester M27 4HA, UK
- Dr Clayton-Smith,Jcs{at}central.cmht.nwest.nhs.uk
- Revised 12 January 2001
- Accepted 13 January 2001
Abstract
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.
