Precocious osteoarthritis in a family with recurrent COL2A1 mutation.
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.
Carlson
Kerri M
KM
Shriners Hospital for Children and John A. Burns School of Medicine, University of Hawaii, Honolulu 96826-1099, USA.
Yamaga
Karen M
KM
Reinker
Kent A
KA
Hsia
Yujen E
YE
Carpenter
Clyde
C
Abe
Lucienne M
LM
Perry
Andrea K
AK
Person
Donald A
DA
Marchuk
Douglas A
DA
Raney
Ellen M
EM
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
C499177:COL2A1 protein, human; D024043:Collagen Type II; D001120:Arginine; D003545:Cysteine