Childhood-onset osteoarthritis, tall stature, and sensorineural hearing loss associated with Arg75-Cys mutation in procollagen type II gene (COL2A1).
OBJECTIVE
To define the clinical, radiologic, and molecular genetic characteristics of a family with early progressive osteoarthritis mimicking childhood rheumatoid arthritis, Scheuermann-like changes of the spine, tall stature, short 3 and 4 metatarsals, and moderate sensorineural hearing loss.


METHODS
We describe a 22-year-old woman and her 54-year-old mother with early progressive osteoarthritis mimicking childhood rheumatoid arthritis. The index case, her mother, and 3 other family members underwent a physical examination, anthropometric measurements, and radiologic studies. Their DNA was sequenced for the procollagen type II (COL2A1) gene.


RESULTS
Mild scoliosis was noticed in the proband at the age of 6 years, and at the age of 7 years large Schmorl's nodes were found in the vertebrae L1-2. At the age of 11 years, changes resembling Scheuermann's disease were seen, mostly in the thoracic vertebrae. At the same age, she began to have arthralgia in the weight-bearing joints and osteoarthritis progressed fast, necessitating a hip prosthesis at the age of 18 years. The proband and her mother had bilateral sensorineural hearing loss of moderate degree. Both mother and daughter had an Arg75-Cys mutation in the COL2A1 gene.


CONCLUSIONS
This family is the fourth example of the Arg75-Cys mutation in the COL2A1 gene, which appears to lead to a clearly recognizable phenotype. The finding suggests that sensorineural hearing loss may be a part of this syndrome.
Löppönen
Tuija
T
University of Oulu, Oulu, Finland. tuija.lopponen@oulu.fi
Körkkö
Jarmo
J
Lundan
Tuija
T
Seppänen
Ulpu
U
Ignatius
Jaakko
J
Kääriäinen
Helena
H
D000328:Adult; D001120:Arginine / Q000235:genetics; D001171:Arthritis, Juvenile / Q000175:diagnosis; D001827:Body Height; D024043:Collagen Type II / Q000235:genetics* / Q000378:metabolism; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008159:Lumbar Vertebrae / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010003:Osteoarthritis / Q000235:genetics*; D012600:Scoliosis / Q000473:pathology; D013577:Syndrome
C499177:COL2A1 protein, human; D024043:Collagen Type II; D001120:Arginine; D003545:Cysteine