CDKL5 gene status in female patients with epilepsy and Rett-like features: two new mutations in the catalytic domain

BMC Medical Genetics

Research Article

Feliciano Ramos¹  María-Asunción López-Aríztegui²  Cristina Martínez-Bouzas³  María-Isabel Tejada³  Nerea Puente³  Hiart Maortua³  Izaskun Rubio³  Maria-Rosario Domingo⁴  María-Jesús Martínez⁵  Ainhoa García-Ribes⁵  María-Teresa Calvo⁶ 

[1] Consulta de Genética Clínica, Departamento de Pediatría, Hospital Clínico de Zaragoza, Zaragoza, Spain;Laboratorio de Citogenética y Consulta de Consejo Genético, Servicio de Genética, Hospital Universitario Cruces, Barakaldo-Bizkaia, Spain;Laboratorio de Genética Molecular, Servicio de Genética, Hospital Universitario Cruces, Instituto BioCruces, Barakaldo-Bizkaia, Spain;Sección de Neuropediatría del Servicio de Pediatría, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain;Sección de Neuropediatría del Servicio de Pediatría, Hospital de Cruces, Barakaldo-Bizkaia, Spain;Unidad de Genética Médica, Hospital Universitario Miguel Servet, Zaragoza, Spain;

关键词: CDKL5;    Epilepsy;    MECP2;    MLPA;    Rett syndrome;   

DOI  :  10.1186/1471-2350-13-68

 received in 2012-03-02, accepted in 2012-07-25,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMutations in the cyclin-dependent kinase-like 5 gene (CDKL5) located in the Xp22 region have been shown to cause a subset of atypical Rett syndrome with infantile spasms or early seizures starting in the first postnatal months.MethodsWe performed mutation screening of CDKL5 in 60 female patients who had been identified as negative for the methyl CpG-binding protein 2 gene (MECP2) mutations, but who had current or past epilepsy, regardless of the age of onset, type, and severity. All the exons in the CDKL5 gene and their neighbouring sequences were examined, and CDKL5 rearrangements were studied by multiplex ligation-dependent probe amplification (MLPA).ResultsSix previously unidentified DNA changes were detected, two of which were disease-causing mutations in the catalytic domain: a frameshift mutation (c.509_510insGT; p.Glu170GlyfsX36) and a complete deletion of exon 10. Both were found in patients with seizures that started in the first month of life.ConclusionsThis study demonstrated the importance of CDKL5 mutations as etiological factors in neurodevelopmental disorders, and indicated that a thorough analysis of the CDKL5 gene sequence and its rearrangements should be considered in females with Rett syndrome-like phenotypes, severe encephalopathy and epilepsy with onset before 5 months of age. This study also confirmed the usefulness of MLPA as a diagnostic screening method for use in clinical practice.

【 授权许可】

Unknown   
© Maortua et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.