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Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature.
- Source :
-
Clinical genetics [Clin Genet] 2009 Oct; Vol. 76 (4), pp. 357-71. - Publication Year :
- 2009
-
Abstract
- The CDKL5 gene has been implicated in the molecular etiology of early-onset intractable seizures with infantile spasms (IS), severe hypotonia and atypical Rett syndrome (RTT) features. So far, 48 deleterious alleles have been reported in the literature. We screened the CDKL5 gene in a cohort of 177 patients with early-onset seizures, including 30 men and 10 girls with Aicardi syndrome. The screening was negative for all men as well as for women with Aicardi syndrome, excluding the CDKL5 gene as a candidate for this neurodevelopmental disorder. We report 11 additional de novo mutations in CDKL5 in female patients. For the first time, the MLPA approach allowed the identification of a partial deletion encompassing the promoter and the first two exons of CDKL5. The 10-point mutations consist of five missenses (with recurrent amino acid changes at p.Ala40 and p.Arg178), four splicing variants and a 1-base pair duplication. We present a review of all mutated alleles published in the literature. In our study, the overall frequency of mutations in CDKL5 in women with early-onset seizures is around 8.6%, a result comparable with previous reports. Noteworthy, the CDKL5 mutation rate is high (28%) in women with early-onset seizures and IS.
- Subjects :
- Blotting, Western
Cells, Cultured
Child, Preschool
DNA Primers genetics
Female
Flow Cytometry
France
Gene Frequency
Genetic Testing
Humans
Infant
Infant, Newborn
Pedigree
Reverse Transcriptase Polymerase Chain Reaction
Genetic Predisposition to Disease genetics
Mutation genetics
Phenotype
Protein Serine-Threonine Kinases genetics
Rett Syndrome genetics
Seizures genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1399-0004
- Volume :
- 76
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Clinical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 19793311
- Full Text :
- https://doi.org/10.1111/j.1399-0004.2009.01194.x