Mutation screening of the CDKL5 gene in cryptogenic infantile intractable epilepsy and review of clinical sensitivity

作者：Intusoma Utcharee; Hayeeduereh Fadell; Plong On Oradawan; Sripo Thanya; Vasiknanonte Punnee; Janjindamai Supachai; Lusawat Apasri; Thammongkol Sasipa; Visudtibhan Anannit; Limprasert Pornprot^*

来源：European Journal of Paediatric Neurology, 2011, 15(5): 432-438.

DOI：10.1016/j.ejpn.2011.01.005

• Cyclin-dependent kinase-like 5 gene
• Epilepsy
• Mental retardation
• Sensitivity
• Thailand

Purposes: To perform CDKL5 mutation screening in Thai children with cryptogenic infantile intractable epilepsy and to determine the clinical sensitivity of CDKL5 screening when different inclusion criteria were applied.
Methods: Children with cryptogenic infantile intractable epilepsy were screened for CDKL5 mutation using multiplex ligation-dependent probe amplification and DNA sequencing. The clinical sensitivity was reviewed by combining the results of studies using similar inclusion screening criteria.
Results: Thirty children (19 girls and 11 boys) with a median seizure onset of 7 months were screened. Almost a half had infantile spasms and one fifth had stereotypic hand movements. A novel c.2854C>T (p.R952X) was identified in an ambulatory girl who had severe mental retardation, multiple types of seizures without Rett-like features. Her mother had a mild intellectual disability, yet her grandmother and half sister were normal despite having the same genetic alteration (random X-inactivation patterns). The pathogenicity of p.R952X identified here was uncertain since healthy relatives and 6 female controls also harbor this alteration. The clinical sensitivity of CDKL5 mutation screening among females with Rett-like features and negative MECP2 screening was 7.8% while the clinical sensitivity among females having cryptogenic intractable seizures with an onset before the ages of 12, 6 and 3 months were 4.7, 11.6 and 14.3%, respectively.

• 出版日期2011-9