Molecular genetics of human primary microcephaly: an overview

Muhammad Faheem, Muhammad Imran Naseer, Mahmood Rasool, Adeel G Chaudhary, Taha A Kumosani, Asad Muhammad Ilyas, Peter Natesan Pushparaj, Farid Ahmed, Hussain A Algahtani, Mohammad H Al-Qahtani, Hasan Saleh Jamal
2015 BMC Medical Genomics  
Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been
more » ... ped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder.
doi:10.1186/1755-8794-8-s1-s4 pmid:25951892 pmcid:PMC4315316 fatcat:zlhvh4qssfh73cgjr7rqclwwey