title: Precocious osteoarthritis in a family with recurrent COL2A1 mutation.
abstract: OBJECTIVE
  To examine the genotypic and phenotypic characteristics of a Micronesian kindred with autosomal dominant precocious osteoarthritis (OA).
  
  
  METHODS
  We reviewed records and radiographs of 3 index patients and their parents, administered questionnaires to 16 additional kindred members, performed whole-genome scans of 24 family members, and sequenced relevant genes from 16 family members.
  
  
  RESULTS
  The kindred displayed early onset OA, enlarged epiphyses, platyspondyly, and brachydactyly with dysplastic findings consistent with mild spondyloepiphyseal dysplasia. Genetic analysis revealed an arginine to cysteine substitution at position 75 of the collagen 2A1 gene, a mutation that has been described in 4 other geographically distinct families. The major phenotypic differences among the families were in height (ranging from short to tall) and hearing loss noted in 3 of the 5 families.
  
  
  CONCLUSIONS
  The presence of the COL2A1 Arg75Cys mutation in 5 geographically distinct areas helps to confirm a potential mutational hotspot. The diverse phenotypic spectrum suggests that modifier genes and environmental factors play a role in the expression of this mutation.
authors.affiliation: Shriners Hospital for Children and John A. Burns School of Medicine, University of Hawaii, Honolulu 96826-1099, USA.
authors.forename: Kerri M
authors.initials: KM
authors.lastname: Carlson
authors.forename: Karen M
authors.initials: KM
authors.lastname: Yamaga
authors.forename: Kent A
authors.initials: KA
authors.lastname: Reinker
authors.forename: Yujen E
authors.initials: YE
authors.lastname: Hsia
authors.forename: Clyde
authors.initials: C
authors.lastname: Carpenter
authors.forename: Lucienne M
authors.initials: LM
authors.lastname: Abe
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Perry
authors.forename: Donald A
authors.initials: DA
authors.lastname: Person
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Marchuk
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Raney
mesh_terms: D001120:Arginine / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D020125:Mutation, Missense / Q000235:genetics*; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011859:Radiography
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D001120:Arginine; D003545:Cysteine