Normal early development in siblings with novel compound heterozygous variants in ASPM

Autosomal recessive primary microcephaly 5 (MCPH5) is caused by pathogenic variants in ASPM . Using whole-exome sequencing, we diagnosed two siblings with MCPH5. A known pathogenic variant (NM_018136.4: c.9697C > T, p.(Arg3233*)) and a novel pathogenic variant (c.1402_1406del, p.(Asn468Serfs*2)) of ASPM were identified in affected siblings with normal intelligence. Their pathogenic variants were not located in the critical regions of ASPM , but the relationship between the genotypes and their normal intelligence was unclear.