Intriguingly, the string of 41 miscoded amino acids (p.(Glu913Argfs*42)) in our patients nearly completely overwrites the second PEST domain (amino acid residues 911–932), which may hinder its function in protein cleavage at a specific developmental stage of the brain, thereby drastically affecting the proliferation and differentiation of the NPC pool and in turn resulting in microcephaly. The gene discussed is NPC1; the disease is microcephaly.