Autosomal recessive primary microcephaly (MCPH) is a very rare neuro-developmental disease with brain size reduction. More than a dozen loci encoding proteins of diverse function have been shown to be responsible for MCPH1-13. Mutations in the D40/KNL1/CASC5 gene, which was initially characterized as a gene involved in chromosomal translocation in leukemia and as a member of the cancer/testis gene family, was later found to encode a kinetochore protein essential for mitotic cell division and to cause MCPH4. Although our previous studies showed that this gene is required for cell growth and division in vitro and in animal experiments, the revelation that mutations in this gene caused microcephaly provides in vivo evidence of a critical role in brain growth. In this review, we describe mutated gene targets responsible for MCPH1-13 and summarize clinical studies of, and molecular and biological aspects of the gene and encoded protein responsible for MCPH4.
Keywords: CASC5; D40; MCPH4; cancer/testis; kinetochore.
© 2017 Japanese Teratology Society.