Variant "CDKL5:c.1403G-C(p.S468T)"
Search result: 1 record
Variant information
Gene:
CDKL5 
Variant:
CDKL5:c.1403G-C(p.S468T) 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
1 
Disorder:
1 
Reference:
1 
Effect type:
Expressivity(1)  
Modifier effect:
Risk factor(1)  
Detail：
  • Target disease:
    West syndrome (Orphanet_3451)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    Assessment of genotype–phenotype associations and bioinformatics analysis 
    Effect:
    Complex genotype composed of different combinations of mutations in each patient seems to be related to the phenotype variability.
    Reference:
    PMID28780406
    Title:
    Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state.
    Species studied:
    Human
    Abstract:
    INTRODUCTION:West syndrome is a rare epileptic encephalopathy of early infancy, characterized by epileptic spasms, hypsarrhythmia, and psychomotor retardation beginning in the first year of life. METHODS:The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients. RESULTS:The results revealed a complex genotype with more than one mutation in each patient including the known mutations c.1910C>G (P2, P3); c.2372A>C in P3 and c.2395C>G in P1 and novel variants including c.616G>A, shared by the three patients P1, P2 and P3; c.1403G>C shared by P2 and P3 and c.2288A>G in patient P1. CONCLUSIONS:All the mutations were at somatic mosaic state and were de novo in the patients except ones (c.2372A>C). To our knowledge; the somatic mosaic state is described for the first time in patients with West syndrome. Five identified mutations were located in the C-terminal domain of the protein, while the novel mutation (c.616G>A) was in the catalytic domain. Bioinformatic tools predicted that this latter is the most pathogenic substitution affecting 3D protein structure and the secondary mRNA structure. Complex genotype composed of different combinations of mutations in each patient seems to be related to the phenotype variability.