Skip to main content Accessibility help
×
Home
Hostname: page-component-78bd46657c-fstz4 Total loading time: 0.168 Render date: 2021-05-07T11:19:58.772Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false, "newCitedByModal": true }

Cyclin-Dependent Kinase-Like 5 (CDKL5) Mutation Screening in Rett Syndrome and Related Disorders

Published online by Cambridge University Press:  21 February 2012

Rose White
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics & Child Health, University of Sydney, Australia.
Gladys Ho
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics & Child Health, University of Sydney, Australia.
Swetlana Schmidt
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia; University of Applied Sciences, Mannheim, Germany.
Ingrid E. Scheffer
Affiliation:
Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia.
Alexandra Fischer
Affiliation:
Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia.
Simone C. Yendle
Affiliation:
Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia.
Thierry Bienvenu
Affiliation:
Université Paris Descartes, Institut Cochin, CNRS (UMR8104), Inserm, U567, Paris, France.
Juliette Nectoux
Affiliation:
Université Paris Descartes, Institut Cochin, CNRS (UMR8104), Inserm, U567, Paris, France.
Carolyn J. Ellaway
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics & Child Health, University of Sydney, Australia.
Artur Darmanian
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia.
XingZhang Tong
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia.
Desiree Cloosterman
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia.
Bruce Bennetts
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics & Child Health, University of Sydney, Australia.
Veena Kalra
Affiliation:
Department of Pediatrics, All-India Institute of Medical Sciences, New Delhi, India.
Tod Fullston
Affiliation:
Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia; Department of Paediatrics, University of Adelaide, Adelaide, Australia.
Jozef Gecz
Affiliation:
Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia; Department of Paediatrics, University of Adelaide, Adelaide, Australia.
Timothy C. Cox
Affiliation:
Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
John Christodoulou
Affiliation:
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics & Child Health, University of Sydney, Australia. johnc@chw.edu.au
Corresponding
E-mail address:

Abstract

Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting females almost exclusively and is characterized by a wide spectrum of clinical manifestations. Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene have been found in up to 95% of classical RTT cases and a lesser proportion of atypical cases. Recently, mutations in another X-linked gene, CDKL5 (cyclin-dependent kinase-like 5) have been found to cause atypical RTT, in particular the early onset seizure (Hanefeld variant) and one female with autism. In this study we screened several cohorts of children for CDKL5 mutations, totaling 316 patients, including individuals with a clinical diagnosis of RTT but who were negative for MECP2 mutations (n = 102), males with X-linked mental retardation (n = 9), patients with West syndrome (n = 52), patients with autism (n = 59), patients with epileptic encephalopathy (n = 33), patients with Aicardi syndrome (n = 7) and other patients with intellectual disability with or without seizures (n = 54). In all, seven polymorphic variations and four de novo mutations (c.586C>T [p.S196L]; c.58G>C [p.G20R]; c.2504delC [p.P835fs]; deletion of exons 1 - 3) were identified, and in all instances of the latter the clinical phenotype was that of an epileptic encephalopathy. These results suggest that pathogenic CDKL5 mutations are unlikely to be identified in the absence of severe early-onset seizures and highlight the importance of screening for large intragenic and whole gene deletions.

Type
Articles
Copyright
Copyright © Cambridge University Press 2010
You have Access

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Cyclin-Dependent Kinase-Like 5 (CDKL5) Mutation Screening in Rett Syndrome and Related Disorders
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Cyclin-Dependent Kinase-Like 5 (CDKL5) Mutation Screening in Rett Syndrome and Related Disorders
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Cyclin-Dependent Kinase-Like 5 (CDKL5) Mutation Screening in Rett Syndrome and Related Disorders
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *