CDK5 was originally reported in cases of lissencephaly 7 with cerebellar hypoplasia in 2015 (PMID: 25560765). This initial report included a large consanguineous family with 10 affected individuals, 4 of them were genetically studied, and found to have homozygous IVS8+1G>A (c.580+1G>A). Linkage study of this family identified a candidate region on 7q35-q36.1, with a maximum multipoint LOD score of 4.87. Targeted sequencing of CDK5 was followed by exome sequencing of one affected individual to identify the variant. RNA and protein studies using the fibroblasts of an affected individual confirmed a lack of wild-type CDK5 RNA and protein products. A knockout mouse model (PMID: 8855328), CRISPR/Cas9-based knockdown of Cdk5 in the ferret brain (PMID: 28854363) and a functional study of the role of Cdk5 on another lissencephaly gene, Dcx (PMID: 14741103) were scored as functional evidence. In total, it was interpreted that there is moderate level of evidence to suggest that theCDK5 gene is related to to lissencephaly 7 with cerebellar hypoplasia. This curation was approved by the Brain Malformation Panel on 07/11/2023.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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