Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4353708 | Progress in Neurobiology | 2010 | 21 Pages |
Abstract
Autosomal recessive primary microcephaly (MCPH), historically referred to as Microcephalia vera, is a genetically and clinically heterogeneous disease. Patients with MCPH typically exhibit congenital microcephaly as well as mental retardation, but usually no further neurological findings or malformations. Their microcephaly with grossly preserved macroscopic organization of the brain is a consequence of a reduced brain volume, which is evident particularly within the cerebral cortex and thus results to a large part from a reduction of grey matter. Some patients with MCPH further provide evidence of neuronal heterotopias, polymicrogyria or cortical dysplasia suggesting an associated neuronal migration defect. Genetic causes of MCPH subtypes 1-7 include mutations in genes encoding microcephalin, cyclin-dependent kinase 5 regulatory associated protein 2 (CDK5RAP2), abnormal spindle-like, microcephaly associated protein (ASPM), centromeric protein J (CENPJ), and SCL/TAL1-interrupting locus (STIL) as well as linkage to the two loci 19q13.1-13.2 and 15q15-q21. Here, we provide a timely overview of current knowledge on mechanisms leading to microcephaly in humans with MCPH and abnormalities in cell division/cell survival in corresponding animal models. Understanding the pathomechanisms leading to MCPH is of high importance not only for our understanding of physiologic brain development (particularly of cortex formation), but also for that of trends in mammalian evolution with a massive increase in size of the cerebral cortex in primates, of microcephalies of other etiologies including environmentally induced microcephalies, and of cancer formation.
Keywords
GLI1LAPMicrocephalinCPAPMCPHPLK1ReelinTbr1RELNNBS1TNFalphaMcph1PCNTmDC1BubR1BRCT53BP1Pitx2BACH1CDK5RAP2glioma-associated oncogene homologataxia telangiectasia and Rad3-related proteinPCMCMDATRPCCPericentrinshRNASTILγTuRCcentrosominEB1cell division cycle 25AASPMSufuAPCcdk5OFCataxia telangiectasia mutatedshort hairpin RNASpindlestandard deviationPremature chromosome condensationtumor necrosis factor-alphaATMShhcalponin homology domainMOTCNSCentrosomesuppressor of fusedCNNcentral nervous systemcyclin-dependent kinase 5sonic hedgehogPaired-like homeodomain transcription factor 2Mad2microtubule-organizing centermicrocephalyNeuroepitheliummediator of DNA damage checkpoint protein 1Polo-like kinase 1anaphase-promoting complexCell cycleCASKCalmodulinMental retardation
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Authors
Angela M. Kaindl, Sandrine Passemard, Pavan Kumar, Nadine Kraemer, Lina Issa, Angelika Zwirner, Benedicte Gerard, Alain Verloes, Shyamala Mani, Pierre Gressens,