A Novel Variant c.149G>A in CDK5 Gene Causing Lissencephaly Type 7
Amita Moirangthem1, Anjana Kar2, Mahima Sagar3
1Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India.
Clinical Genetics
|April 5, 2025
Summary
This study identifies a new CDK5 gene variant causing lissencephaly type 7, a severe brain malformation. The findings expand our understanding of the genetic causes of lissencephaly and its associated neurological deficits.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Lissencephaly is a severe brain malformation characterized by a smooth cerebral surface due to defective neuronal migration.
- Cyclin-dependent kinase 5 (CDK5) is crucial for neuronal development, and its dysfunction is linked to neurodevelopmental disorders.
- Lissencephaly type 7, caused by CDK5 variants, has been reported in only one family previously.
Purpose of the Study:
- To report a novel case of lissencephaly type 7 in an infant with a new CDK5 variant.
- To investigate the functional impact of the identified CDK5 variant.
Main Methods:
- Clinical evaluation of an infant with severe brain malformations.
- Genetic sequencing to identify variants in the CDK5 gene.
- In silico analysis and yeast complementation assays to assess variant pathogenicity.
Main Results:
- A novel homozygous missense variant (c.149G>A, p.Arg50Gln) in CDK5 was identified in the affected infant.
- The infant presented with diffuse agyria, cerebellar hypoplasia, agenesis of the corpus callosum, refractory seizures, microcephaly, and developmental failure.
- In silico and functional analyses indicated that the p.Arg50Gln variant disrupts CDK5 protein structure and function.
Conclusions:
- This is the second family identified with CDK5-related lissencephaly type 7.
- The findings highlight the role of CDK5 in human brain development and expand the spectrum of lissencephaly-associated genetic defects.
Keywords:
agenesis of corpus callosumagyriacerebellar hypoplasiagrowth assaylissencephalyrefractory seizuresyeast complementation assayMore Related Videos
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