A novel de novo variant of CDKL5 in an Iranian child with infantile-onset refractory epilepsy.
Noorodin Karami, Mohammadreza Dehghani, Samira Asadollahi et al.
✦ AI-curated · Sources linked
Case in brief
An Iranian girl presented with developmental delay, hypotonia, and refractory seizures. Whole-exome sequencing identified a de novo CDKL5 frameshift variant, c.1037_1038delTCinsCAGATCTAA (p.Ile346Thrfs*14), which Sanger sequencing validated and was classified as pathogenic under ACMG criteria. The variant was predicted to introduce a premature stop codon, substantially shorten the protein, and remove essential functional domains. Treatment with valproate and lamotrigine was associated with a considerable reduction in seizure number.
What made this case unusual
The case identified a novel de novo CDKL5 frameshift variant predicted to truncate the protein and remove essential functional domains.
Diagnostic / clinical pearl
In a child with developmental delay and refractory seizures, sequencing can identify a genetic cause; confirmatory testing and variant interpretation can support early diagnosis.