title: Mutations in the pre-replication complex cause Meier-Gorlin syndrome.
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.
authors.affiliation: Medical Research Council (MRC) Human Genetics Unit (HGU), Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
authors.forename: Louise S
authors.initials: LS
authors.lastname: Bicknell
authors.forename: Ernie M H F
authors.initials: EM
authors.lastname: Bongers
authors.forename: Andrea
authors.initials: A
authors.lastname: Leitch
authors.forename: Stephen
authors.initials: S
authors.lastname: Brown
authors.forename: Jeroen
authors.initials: J
authors.lastname: Schoots
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Harley
authors.forename: Salim
authors.initials: S
authors.lastname: Aftimos
authors.forename: Jumana Y
authors.initials: JY
authors.lastname: Al-Aama
authors.forename: Michael
authors.initials: M
authors.lastname: Bober
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Brown
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: John
authors.initials: J
authors.lastname: Dean
authors.forename: Alaa Y
authors.initials: AY
authors.lastname: Edrees
authors.forename: Murray
authors.initials: M
authors.lastname: Feingold
authors.forename: Alan
authors.initials: A
authors.lastname: Fryer
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Kau
authors.forename: Nine V A M
authors.initials: NV
authors.lastname: Knoers
authors.forename: James
authors.initials: J
authors.lastname: Mackenzie
authors.forename: John M
authors.initials: JM
authors.lastname: Opitz
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Alison
authors.initials: A
authors.lastname: Ross
authors.forename: I Karen
authors.initials: IK
authors.lastname: Temple
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wise
authors.forename: Michael
authors.initials: M
authors.lastname: Wright
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Jackson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics; D065817:Congenital Microtia; D017931:DNA Primers / Q000235:genetics; D004423:Ear / Q000002:abnormalities / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation; D006130:Growth Disorders / Q000235:genetics / Q000473:pathology; D006239:Haplotypes; D006801:Humans; D008297:Male; D008844:Micrognathism / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics; D051738:Origin Recognition Complex / Q000235:genetics*; D010329:Patella / Q000002:abnormalities / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017386:Sequence Homology, Amino Acid
chemical_list: C103706:CDC6 protein, human; C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D017931:DNA Primers; D009687:Nuclear Proteins; C497223:ORC1 protein, human; C109152:ORC4 protein, human; C497227:ORC6 protein, human; D051738:Origin Recognition Complex