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

BMC Medical Genetics

María-Isabel Tejada⁴  Izaskun Rubio⁴  Nerea Puente⁴  María-Asunción López-Aríztegui⁶  María-Jesús Martínez¹  Ainhoa García-Ribes¹  Feliciano Ramos⁵  Maria-Rosario Domingo²  María-Teresa Calvo³  Cristina Martínez-Bouzas⁴  Hiart Maortua⁴ 

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

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

Others  :  1177818
DOI  :  10.1186/1471-2350-13-68

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

【 摘 要 】

Background

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.

Methods

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).

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Maortua et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1 .

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