Using homozygosity mapping complemented with whole-exome, gene panel or Sanger sequencing, we identified 12 novel mutations in 3 known MCPH-associated genes - 9 in ASPM, 2 in MCPH1 and 1 in CDK5RAP2.
Autosomal Recessive Primary Microcephaly (MCPH) is one of those, for which seven loci (MCPH1-MCPH7) with the corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL) have been reported so far.
WDR62 is one of seven genes responsible for autosomal recessive primary microcephaly (MCPH), and appears to be one of the most frequently involved in MCPH following ASPM.
Genotyping using polymorphic microsatellite markers linked to 7 autosomal recessive primary microcephaly loci revealed linkage of 18 families to the MCPH5 locus.
They also suggest that low birth weight may be a feature of MCPH, a finding that needs confirmation, and confirm that ASPM mutations are associated with simplified cortical gyration.
Homozygous mutations in the ASPM gene, located at MCPH5 locus on chromosome 1q31, are the most common cause of MCPH particularly in the Pakistani population.
Genotyping using microsatellite markers linked to the six known MCPH loci showed the linkage of 18 families to the MCPH5 locus, two to the MCPH2 locus, two to the MCPH4 locus, and one to the MCPH6 locus.
Human autosomal recessive primary microcephaly (MCPH) is a heterogeneous disorder with at least six genetic loci (MCPH1-6), with MCPH5, caused by ASPM mutation, being the most common.
Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation.
Here we show that the most common cause of MCPH is homozygous mutation of ASPM, the human ortholog of the Drosophila melanogaster abnormal spindle gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts.
Autosomal recessive primary microcephaly-5 (MCPH5) is characterized by congenital microcephaly and is caused by the mutation in the abnormal spindle-like, microcephaly-associated (ASPM) gene.
Finally, a hypomorphic mutation identified in ASPMmicrocephaly patients similarly caused spindle pole unfocusing in the absence of CDK5RAP2, suggesting a possible link between spindle pole disorganisation and microcephaly.
We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ, MCPH1) across 21 species representing all major clades of anthropoid primates.