Molecular and cellular basis of autosomal recessive primary microcephaly

Biomed Res Int. 2014;2014:547986. doi: 10.1155/2014/547986. Epub 2014 Dec 8.

Abstract

Autosomal recessive primary microcephaly (MCPH) is a rare hereditary neurodevelopmental disorder characterized by a marked reduction in brain size and intellectual disability. MCPH is genetically heterogeneous and can exhibit additional clinical features that overlap with related disorders including Seckel syndrome, Meier-Gorlin syndrome, and microcephalic osteodysplastic dwarfism. In this review, we discuss the key proteins mutated in MCPH. To date, MCPH-causing mutations have been identified in twelve different genes, many of which encode proteins that are involved in cell cycle regulation or are present at the centrosome, an organelle crucial for mitotic spindle assembly and cell division. We highlight recent findings on MCPH proteins with regard to their role in cell cycle progression, centrosome function, and early brain development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins
  • Centrosome / ultrastructure
  • Cytoskeletal Proteins
  • Genetic Heterogeneity
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Microcephaly / genetics
  • Microcephaly / physiopathology
  • Microtubule-Associated Proteins / genetics*
  • Multiprotein Complexes / genetics
  • Mutation
  • Nerve Tissue Proteins / genetics*

Substances

  • ASPM protein, human
  • CDK5RAP2 protein, human
  • CENPJ protein, human
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Knl1 protein, human
  • MCPH1 protein, human
  • Microtubule-Associated Proteins
  • Multiprotein Complexes
  • Nerve Tissue Proteins

Supplementary concepts

  • Autosomal Recessive Primary Microcephaly