Relevance to Autism

A de novo missense variant in the ASPM gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. Rare inherited loss-of-function and damaging missense variants in the ASPM gene were identified in ASD probands from the Simons Simplex Collection in Krumm et al., 2015 and in a cohort of Chinese ASD probands in Guo et al., 2017. Subsequent Transmission and De Novo Association (TADA) analysis in Guo et al., 2017 identified ASPM as an ASD candidate gene, with a PTADA of 0.001826 in the Chinese ASD case-control cohort and a PTADA of 0.001356 in a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Molecular Function

This gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. Studies in mouse also suggest a role of this gene in mitotic spindle regulation, with a preferential role in regulating neurogenesis. Biallelic mutations in the ASPM gene are responsible for a form of autosomal recessive primary microcephaly (MCPH5; OMIM 608716), a disorder associated with intellectual disability and speech delay (Bond et al., 2002; Bond et al., 2003).

External Links

References

Model Summary

Mice with a truncating Aspm1â??7 truncation mutation show impaired short- and long-term object recognition memory, increased place learning, ventriculomegaly, corpus callosum dysgenesis and decreased parvalbumin (PV)+ interneuron numbers in the hippocampal CA regions and thalamic reticular nucleus.

References