Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome

Nat Genet. 2011 Feb 27;43(4):360-4. doi: 10.1038/ng.777.


Meier-Gorlin syndrome is a rare autosomal recessive genetic condition whose primary clinical hallmarks include small stature, small external ears and small or absent patellae. Using marker-assisted mapping in multiple families from a founder population and traditional coding exon sequencing of positional candidate genes, we identified three different mutations in the gene encoding ORC4, a component of the eukaryotic origin recognition complex, in five individuals with Meier-Gorlin syndrome. In two such individuals that were negative for mutations in ORC4, we found potential mutations in ORC1 and CDT1, two other genes involved in origin recognition. ORC4 is well conserved in eukaryotes, and the yeast equivalent of the human ORC4 missense mutation was shown to be pathogenic in functional assays of cell growth. This is the first report, to our knowledge, of a germline mutation in any gene of the origin recognition complex in a vertebrate organism.

Publication types

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

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Base Sequence
  • Cell Cycle Proteins / genetics*
  • Child
  • Child, Preschool
  • Congenital Microtia
  • Consanguinity
  • Conserved Sequence
  • DNA / genetics
  • Ear / abnormalities
  • Ear / pathology
  • Female
  • Founder Effect
  • Growth Disorders / genetics
  • Growth Disorders / pathology
  • Haplotypes
  • Humans
  • Male
  • Micrognathism / genetics
  • Micrognathism / pathology
  • Molecular Sequence Data
  • Mutation*
  • Origin Recognition Complex / genetics*
  • Patella / abnormalities
  • Patella / pathology
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Sequence Homology, Amino Acid


  • CDT1 protein, human
  • Cell Cycle Proteins
  • ORC1 protein, human
  • ORC4 protein, human
  • Origin Recognition Complex
  • DNA

Supplementary concepts

  • Meier-Gorlin syndrome

Associated data

  • RefSeq/NM_002552
  • RefSeq/NM_004153
  • RefSeq/NM_030928
  • RefSeq/NP_002543
  • RefSeq/NP_004144
  • RefSeq/NP_112190
  • RefSeq/NP_989577