Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state

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. The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients....

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Bibliographic Details
Published in:Clinica chimica acta 2017-10, Vol.473, p.51-59
Main Authors: Jdila, Marwa Ben, Issa, Abir Ben, Khabou, Boudour, Rhouma, Bochra Ben, Kamoun, Fatma, Ammar-Keskes, Leila, Triki, Chahnez, Fakhfakh, Faiza
Format: Article
Language:English
Subjects:
Adolescent
CDKL5 gene
Child
Child, Preschool
Genotype
Humans
Infant
Male
Mutation
Novel mutations
Phenotype
Protein-Serine-Threonine Kinases - genetics
RNA, Messenger - genetics
RNA, Messenger - metabolism
Somatic mosaic
Spasms, Infantile - genetics
West syndrome (WS)
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Summary: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. The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients. 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. 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. •Novel mutation p.D206N in catalytic domain and other variations in Ct domain were identified in patients with West Syndrome.•The results revealed a complex genotype with more than one mutation in each patient.•All variations were at somatic mosaic state, described for the first time in the West Syndrome
ISSN:0009-8981
1873-3492
DOI:10.1016/j.cca.2017.08.001