primary microcephaly
Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by two principal features, microcephaly present at birth and nonprogressive mental retardation. It causes a great reduction in brain growth in utero.
The microcephaly is the consequence of a small but architecturally normal brain, and it is the cerebral cortex that shows the greatest size reduction.
MCPH is hypothesized to be a primary disorder of neurogenic mitosis, leading to reduced neuron number. Hence, MCPH proteins are likely to be important components of cellular pathways regulating human brain size.
At least six genes can cause this disorder and four of these have recently been identified: autosomal recessive primary microcephaly 1 (MCPH1), abnormal spindle-like, microcephaly associated (ASPM), cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) and centromere protein J (CENPJ).
Whereas aberration of ASPM is the most common cause of MCPH, MCPH1 patients can be more readily diagnosed by the finding of increased numbers of "prophase-like cells" on routine cytogenetic investigation.
Three MCPH proteins are centrosomal components but have apparently diverse roles that affect mitosis. There is accumulating evidence that evolutionary changes to the MCPH genes have contributed to the large brain size seen in primates, particularly humans.
Types
autosomal recessive primary microcephaly (MCPH)
Etiology
There are at least seven MCPH loci.
- Locus MCPH1: MCPH1 (encoding microcephalin)
- Locus MCPH2
- Locus MCPH3: CDK5RAP2
- Locus MCPH4
- Locus MCPH5: ASPM
- Locus MCPH6: CENPJ
- Locus MCPH7
References
Cox J, Jackson AP, Bond J, Woods CG. What primary microcephaly can tell us about brain growth. Trends Mol Med. 2006 Aug;12(8):358-66. PMID: #16829198#
Ponting C, Jackson AP. Evolution of primary microcephaly genes and the enlargement of primate brains. Curr Opin Genet Dev. 2005 Jun;15(3):241-8. PMID: #15917198#
Woods CG, Bond J, Enard W. Autosomal Recessive Primary Microcephaly (MCPH): A Review of Clinical, Molecular, and Evolutionary Findings. Am J Hum Genet. 2005 May;76(5):717-28. PMID: #15806441#