Early‐onset osteoarthritis linked to the type ii procollagen gene. detailed clinical phenotype and further analyses of the gene

Abstract

Objective. To specify in detail the clinical phenotype in 2 Finnish families demonstrating linkage between the type I1 procollagen gene (COL2A1) and osteoarthritis (OA). We also reevaluated the linkage and screened the exon sequences of the COL2Al gene for mutations.Methods. We used single-stranded conformation polymorphism and denaturing gradient-gel electrophoresis techniques for the analyses.Results. Osteoarthritis (OA) is a very common disease which varies in its manifestations. Although most cases are of limited clinical significance, millions of people world-wide become disabled because of OA. Symptoms of pain, stiffness, and limitation of motion are localized to the affected joints. The end result of the process can be grossly deformed joints. The main radiographic features are narrowing of the joint space indicating loss of cartilage, subchondral bone sclerosis, and osteophyte formation in the margins of the bones. The distal interphalangeal joints, hips, knees, the first metatarsophalangeal joints, and the lower lumbar and cervical vertebrae are most commonly affected. Different subsets of the disease can be identified, according to which joints are affected, but the subsets frequently overlap.In some instances, there is an identifiable cause, such as trauma or congenital malformation, but very often, the etiology remains unknown. OA is not an inevitable result of aging; there are elderly people who have no evidence of the disease. Since familial aggregation is seen, genetic factors may be important, particularly in OA of the hand (1,2).

Evaluation of the Relationship Between Hand Osteoarthritis and Osteoporosis in Postmenauposal Women

“…İyi bilinen risk faktörleri arasında yaş, kadın cinsiyet, travma hikayesi ve aile hikayesi yer almaktadır (22)(23)(24)(25) (29). Metakarp bölgesindeki bu lokal kemik kütlesi kaybı iki mekanizmayla açıklanmaya çalışılmıştır.…”

Genetic Association and Linkage Studies in Osteoarthritis

“…a Association for early onset OA; 3 Association for joint involvement and disease severity; *G = generalized; Ha = hand; K = knee; H = hip; na = not available; population based study; HT=haplotype, A27=27 repeats;** = permutation based; *** = including Vaes et al 2008, Southam et al 2007; bold font indicates region with linkage finding The first structural genes analyzed were genes coding for major cartilage collagens II, IX, and XI, where mutations causing Stickler syndrome, a mild chondrodysplasia associated with OA, have been identified (for a review, see Robin et al (2010)). Earlier reports suggested linkage between COL2A1 and OA in two large families (Palotie et al 1989;Vikkula et al 1993), and a causal Arg519Cys mutation in the 1(II) chain was identified in OA families (Ala-Kokko et al 1990;Fertala et al 1997). In addition rare sequence variants in the genes for collagens II and XI have been associated with hip/knee OA (Jakkula et al 2005).…”

“…Similarly as in other complex diseases the early genetic studies in OA focused on rare families and genes known to have a biological role in the development and structure of cartilage (Palotie et al 1989;Ala-Kokko et al 1990;Vikkula et al 1993;Jakkula et al 2005). In the 1990s, the introduction of panels of highly informative microsatellite markers evenly covering the genome allowed hypothesis-free screening with no prior knowledge of the gene functions (Petrukhin et al 1993;Straub et al 1993).…”

“…The genome-wide linkage study approach has been very successful in locating disease-causing genes for monogenic diseases (for example (Kestilä et al 1994;Mäkelä-Bengs et al 1998;Nousiainen et al 2008)). Genes causing rare, familial forms of OA have been identified by genetic linkage studies, which have also revealed novel insight on OA etiology, even though the identified variants have not been significant in predisposing to common forms of OA at the population level (Palotie et al 1989;Ala-Kokko et al 1990;Vikkula et al 1993;Prockop et al 1997;Jakkula et al 2005). In recent years, the knowledge of the human genome has grown substantially.…”

Approach to hand osteoarthritis

“…Popülasyon bazl› ve farkl› ailelerde yap›lan birkaç çal›flmada kromozom 12 üzerin-deki COL2A1 geninin yayg›n OA ile iliflkili oldu¤u gös-terilmifltir. [39][40][41] Örne¤in bir ailede COL2A1'deki tek bir mutasyon, OA's› olan tüm aile fertlerinde saptanm›fl ve OA's› olmayan bireylerde saptanmam›flt›r. COL2A1'deki mutasyon Stickler sendromu ile de iliflkilidir.…”