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last update : 22-02-2012
Symbol MCPH1
Location 8p23.1
Name primary microcephaly 1
Other name(s) premature chromosome condensation syndrome, PCC syndrome (MIM606858)
Corresponding gene MCPH1
Main clinical features
  • mental retardation and congenital microcephaly with a head circumference at least 4 SD below age and sex means, in the absence of other significant malformations or neurological deficits.
  • premature chromosome condensation in the early G2 phase
  • Genetic determination autosomal recessive
    Function/system disorder mental retardation
    Type disease
    Gene product
    Name microcephalin
    Gene mutationChromosome rearrangementEffectComments
    missense     substitution in the N-terminal BRCT domain of MCPH1 with a cellular and clinical phenotype much less pronounced than in truncating mutations
    nonsense   truncated protein Truncating alterations exhibit a distinct cellular phenotype, with a high proportion of prophase-like cells (>10 percent) due to premature chromosome condensation in early G2- and delayed decondensation in early G1-phase of the cell cycle.
  • there are at least seven MCPH loci, and four of the genes have been identified: MCPH1, encoding Microcephalin; MCPH3, encoding CDK5RAP2; MCPH5, encoding ASPM; and MCPH6, encoding CENPJ
  • majority of mutations found in MCPH1 patients harbor premature stop codons, deleting the C-terminal BRCT domains
  • craniosynostosis-microcephaly with chromosomal breakage(CMCB)(MIM218455) is an allelic disorder
  • cells derived from patients with MCPH1 mutations having the premature chromosome condensation (PCC) phenotype (PMID: 21515671))