Open Access Highly Accessed Research article

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

Hiart Maortua1, Cristina Martínez-Bouzas1, María-Teresa Calvo2, Maria-Rosario Domingo3, Feliciano Ramos4, Ainhoa García-Ribes5, María-Jesús Martínez5, María-Asunción López-Aríztegui6, Nerea Puente1, Izaskun Rubio1 and María-Isabel Tejada1*

Author Affiliations

1 Laboratorio de Genética Molecular, Servicio de Genética, Hospital Universitario Cruces, Instituto BioCruces, Barakaldo-Bizkaia, Spain

2 Unidad de Genética Médica, Hospital Universitario Miguel Servet, Zaragoza, Spain

3 Sección de Neuropediatría del Servicio de Pediatría, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain

4 Consulta de Genética Clínica, Departamento de Pediatría, Hospital Clínico de Zaragoza, Zaragoza, Spain

5 Sección de Neuropediatría del Servicio de Pediatría, Hospital de Cruces, Barakaldo-Bizkaia, Spain

6 Laboratorio de Citogenética y Consulta de Consejo Genético, Servicio de Genética, Hospital Universitario Cruces, Barakaldo-Bizkaia, Spain

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BMC Medical Genetics 2012, 13:68  doi:10.1186/1471-2350-13-68

Published: 6 August 2012



Mutations 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.


We 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).


Six 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.


This 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.

CDKL5; Epilepsy; MECP2; MLPA; Rett syndrome