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). Experiments in mice with Clp1 defect showed that these mice had reduced brain weight and volume, as well as reduced thickness of the outer layer of the brain (cortex) and reduced numbers of neurons compared to mice without Clp1 mutation, consistent with microcephaly (small head size). There was an increase in cell death among neuronal progenitor cells (like a stem cell, has a tendency to differentiate into a neuron), which resulted in reduced numbers of cortical neurons.
CLP1