A novel variant of CDK19 causes a severe neurodevelopmental disorder with infantile spasms
Shenghai Yang1, Weishi Yu2, Qian Chen1
1Children's Hospital, Capital Institute of Pediatrics, Beijing, China.
Insights
A novel gene variant, CDK19, is linked to infantile spasms, a severe epilepsy syndrome in infants. This finding expands understanding of the genetic causes of this developmental disorder.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- Infantile spasms are a severe epilepsy syndrome often causing developmental delay in infants.
- Recent studies identified the gene CDK19 as a potential cause of infantile spasms.
Purpose of the Study:
- To report a fifth case of infantile spasms caused by a CDK19 gene variant.
- To further elucidate the role of CDK19 variants in neurodevelopmental disorders.
Main Methods:
- Clinical evaluation of a 10-month-old male patient with infantile spasms.
- Genetic analysis to identify variants in the CDK19 gene.
- Protein structure modeling to assess the impact of the identified variant.
Main Results:
- A novel de novo missense variant (c.92C > A, p.Thr31Asn) in CDK19 was identified and classified as likely pathogenic.
- The patient exhibited clinical features consistent with previously reported cases, with earlier onset of seizures and developmental abnormalities.
- Protein modeling suggested the variant may impair CDK19 kinase activity and transcriptional regulation.
Conclusions:
- This case expands the known genotype spectrum for CDK19-related disorders.
- The findings reinforce that CDK19 missense variants are causative of neurodevelopmental disorders presenting as infantile spasms.
Abstract:
Infantile spasms are a potentially catastrophic form of epilepsy syndrome that are usually associated with substantial developmental delay and commonly occur in children younger than 1 yr. Recent reports on four cases revealed that variants harbored in a novel gene CDK19 were causative for the syndrome. We report a fifth affected individual, a 10-mo-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms. We identified a novel de novo missense variant c.92C > A (p.Thr31Asn) in CDK19 that was classified as a likely pathogenic disease-causing variant. The characterized clinical phenotypes of the proband were similar to the previously reported four patients, but he had few variable features including earlier seizure onset age and earlier occurring developmental abnormality. Protein structure modeling analysis revealed that CDK19 variants may disable its kinase activity, which would further impede the transcriptional regulation, thus leading to detrimental pathologies. Our report expanded CDK19 genotype spectrum and further demonstrated that a CDK19 missense variant was causative of neurodevelopmental disorder clinically marked by infantile spasms.
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