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ASPM (gene)
The ASPM gene contains 28 exons and codes for a 3477 amino‐acid‐long protein. The ASPM protein is conserved across species including human, mouse, Drosophila, and C. elegans.

Human studies
Human primary microcephaly (MCPH) is a distinct subtype that is genetically inherited as an autosomal recessive trait. MCPH is characterized by a smaller cerebral cortex associated with mild to moderate mental retardation and no other neurological deficits. Additionally, MCPH is associated with the absence of environmental causes such as intrauterine infections, exposure to prenatal radiation or drugs, maternal phenylketonuria, and birth asphyxia. MCPH has an incidence rate of 1/30,000 to 1/250,000 in western populations. To date, mutations in six loci and four genes associated with microcephaly have been discovered in humans. ASPM, one of these genes, is found at the MCPH5 locus. The most common cause of MCPH in humans is homozygous genetic mutation of the ASPM gene, orthologous to the Drosophila abnormal spindle gene (asp). In humans, the ASPM gene may play a strong role in the growth of the cerebral cortex. A total of 22 mutations have been discovered in the ASPM gene in individuals from Pakistan, Turkey, Yemen, Saudi Arabia, Jordan, and the Netherlands.

A study completed in Karnataka, South India by Kumar et al. analyzed the genetics of MCPH due to mutations in the ASPM gene. The study included nine families with blood relatives across many familial generations. Kumar et al. performed High‐resolution G‐banding chromosome analysis and haplotype analysis of individuals and families of those affected by MCPH. Kumar et al. found that the South Indian families affected by mutations in the MCPH5 locus did not share a common disease haplotype; thus the authors proposed that different mutations in the ASPM gene are responsible for MCPH.

A similar genetic study of MCPH in Pakistani families was done by Gul et al. in order to evaluate the relationship between ASPM gene mutations and microcephaly. The study was approved by the Institutional Review Board of Quaid-I-Azam University in Islamabad, Pakistan, and involved extraction of DNA and PCR techniques in order to genetically map the ASPM gene. Genotyping using microsatellite regions in the gene revealed that MCPH5 locus mutations were the most common cause of MCPH. Genotyping further linked mutations in the MCPH2 locus, MCPH4 locus, and the MCPH6 locus to microcephaly. Sequence analysis of ASPM in humans revealed four novel mutations; these four types of mutations are an insertion of four nucleotides (9118insCATT), a nonsense mutation (L3080X), a deletion of seven nucleotides (1260delTCAAGTC), and a missense mutation (Q3180P). Gul et al. found that parents who were heterozygous carriers for ASPM had normal cerebral circumferences and normal intelligence levels. The scientists were unable to identify mutations at the MCPH5 locus in nine families who had members affected by MCPH. They concluded that the mutations could be located in the regulatory sequences of ASPM, or that a gene other than ASPM, located in the same region, could be mutated.

The types of mutations causing MCPH in humans was expanded by a study done by Pichon et al. on an individual with primary microcephaly, as the study revealed a translocation breakpoint in the ASPM gene. Pichon et al. obtained BAC clones with BamHI digestion fragments of the "RP11-32D17" insert and used Fluorescence in situ Hybridization (FISH) in order to label the clones with fluorescein-12-dUTP. In order to precisely locate the translocation breakpoint, the BamHI digestion fragments of "RP11-32D17" were analyzed. The translocation breakpoint was located to be within intron 17 of the ASPM gene. The translocation resulted in a truncated ASPM protein, which is most likely a non-functioning protein also seen in truncating point mutations reported in MCPH patients.