Autosomal recessive primary microcephaly-5 (MCPH5) is characterized by congenital microcephaly and is caused by the mutation in the abnormal spindle-like, microcephaly-associated (ASPM) gene.
Finally, a hypomorphic mutation identified in ASPMmicrocephaly patients similarly caused spindle pole unfocusing in the absence of CDK5RAP2, suggesting a possible link between spindle pole disorganisation and microcephaly.
We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ, MCPH1) across 21 species representing all major clades of anthropoid primates.
Here, we report that in Aspm mutant mice, truncated Aspm proteins similar to those causing microcephaly in humans fail to localize to the midbody during M-phase and cause mild microcephaly.
Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly.
Our data suggest that one form of autosomal recessive microcephaly is allelic to at least a subset of microcephaly with simplified gyral pattern, and that the neuronal depletion associated with the ASPM defect predominantly affects the anterior cortex.
Speculations based on studies of the human abnormal-spindle-like, microcephaly-associated (ASPM) gene, the microcephaly primary autosomal recessive (MCPH) gene, and the forkhead box p2 (FOXP2) gene are made and incorporated into what is termed "The pre-FOXP2 Hypothesis of Blood-Injection-Injury Phobia."
Haplotype analysis suggests that the gene causing microcephaly is located between markers D1S3469 and D1S1660, which excludes the previously reported ASPM gene.