Molecular characteristics

All affected individuals in the literature were found to have a homozygous missense sequence variant; CLP1: (NM_006831.2:c.419G > A) resulting in an amino acid substitution of p.(Arg140His), both of which are positively charged polar amino acids. Segregation studies are consistent with autosomal recessive inheritance. Animal studies revealed that kinase-dead Clp1 mice had a reduced brain weight and volume, as well as reduced cortical thickness and reduced numbers of neurons compared to wild type, consistent with microcephaly. Increase in cell death among neuronal progenitor cells, which resulted in reduced numbers of cortical neurons was also noted.