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Brain Dev. 2015 Oct;37(9):911-5. doi: 10.1016/j.braindev.2015.03.002. Epub 2015 Mar 27.

Somatic mosaicism of a CDKL5 mutation identified by next-generation sequencing.

Author information

1
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
2
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: morisada@med.kobe-u.ac.jp.
3
Department of Neurology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
4
Medical Welfare Center Sakura, Sanda, Japan.
5
Kobe University Graduate School of Health Science, Kobe, Japan.

Abstract

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.

KEYWORDS:

CDKL5; Double mutations; Early infantile epileptic encephalopathy (EIEE); Next-generation sequencing; Somatic mosaicism

PMID:
25819767
DOI:
10.1016/j.braindev.2015.03.002
[Indexed for MEDLINE]

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