Somatic mosaicism of a CDKL5 mutation identified by next-generation sequencing
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Updated: Apr 15, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Takeshi Kato1, Naoya Morisada1, Hiroaki Nagase2
1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Insights
A genetic analysis identified two epilepsy-associated variants in a Japanese boy with CDKL5-related encephalopathy. The CDKL5 mutation was likely the primary cause of his severe neurological symptoms.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- CDKL5-related encephalopathy is a severe X-linked disorder causing early infantile epileptic encephalopathy or atypical Rett syndrome.
- Characterized by intractable epilepsy, severe developmental delay, and Rett syndrome-like features, with onset typically in early infancy.
Observation:
- A 5-year-old Japanese boy presented with intractable epilepsy and severe developmental delay since 2 months of age.
- Electroencephalogram revealed sporadic single poly spikes and diffuse irregular poly spikes.
- Genetic analysis was performed using a next-generation sequencing panel.
Findings:
- Two epilepsy-associated single nucleotide variants were identified: CDKL5 p.Ala40Val and KCNQ2 p.Glu515Asp.
- The CDKL5 p.Ala40Val mutation, previously linked to early infantile epileptic encephalopathy, exhibited somatic mosaicism in the patient.
- The KCNQ2 p.Glu515Asp variant, associated with benign familial neonatal seizures-1, was paternally inherited.
Implications:
- The somatic mosaic CDKL5 mutation is considered the primary driver of the patient's neurological phenotype.
- The KCNQ2 variant may also contribute to neurological effects.
- Next-generation sequencing effectively identifies multiple genetic variants in complex neurological disorders.
Introduction:
CDKL5-related encephalopathy is an X-linked dominantly inherited disorder that is characterized by early infantile epileptic encephalopathy or atypical Rett syndrome. We describe a 5-year-old Japanese boy with intractable epilepsy, severe developmental delay, and Rett syndrome-like features. Onset was at 2 months, when his electroencephalogram showed sporadic single poly spikes and diffuse irregular poly spikes.
Methods:
We conducted a genetic analysis using an Illumina® TruSight™ One sequencing panel on a next-generation sequencer.
Results:
We identified two epilepsy-associated single nucleotide variants in our case: CDKL5 p.Ala40Val and KCNQ2 p.Glu515Asp. CDKL5 p.Ala40Val has been previously reported to be responsible for early infantile epileptic encephalopathy. In our case, the CDKL5 heterozygous mutation showed somatic mosaicism because the boy's karyotype was 46,XY. The KCNQ2 variant p.Glu515Asp is known to cause benign familial neonatal seizures-1, and this variant showed paternal inheritance.
Conclusions:
Although we believe that the somatic mosaic CDKL5 mutation is mainly responsible for the neurological phenotype in the patient, the KCNQ2 variant might have some neurological effect. Genetic analysis by next-generation sequencing is capable of identifying multiple variants in a patient.
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