Mutations in the pre-replication complex cause Meier-Gorlin syndrome

Nat Genet. 2011 Feb 27;43(4):356-9. doi: 10.1038/ng.775.

Abstract

Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears¹⁻³. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Cycle Proteins / genetics
  • Congenital Microtia
  • DNA Primers / genetics
  • Ear / abnormalities
  • Ear / pathology
  • Female
  • Frameshift Mutation
  • Growth Disorders / genetics
  • Growth Disorders / pathology
  • Haplotypes
  • Humans
  • Male
  • Micrognathism / genetics
  • Micrognathism / pathology
  • Molecular Sequence Data
  • Mutation*
  • Mutation, Missense
  • Nuclear Proteins / genetics
  • Origin Recognition Complex / genetics*
  • Patella / abnormalities
  • Patella / pathology
  • Pedigree
  • Phenotype
  • Sequence Homology, Amino Acid

Substances

  • CDC6 protein, human
  • CDT1 protein, human
  • Cell Cycle Proteins
  • DNA Primers
  • Nuclear Proteins
  • ORC1 protein, human
  • ORC4 protein, human
  • ORC6 protein, human
  • Origin Recognition Complex

Supplementary concepts

  • Meier-Gorlin syndrome

Associated data

  • RefSeq/NM_001254
  • RefSeq/NM_004153
  • RefSeq/NM_014321
  • RefSeq/NM_030928
  • RefSeq/NM_181742