Further evidence for genetic anticipation in familial rheumatoid arthritis

Objective-To determine whether preliminary evidence supporting features of genetic anticipation in familial rheumatoid arthritis (RA) could be replicated in independent and larger samples. Method-Data were obtained from records of 59 multicase families from the Arthritis and Rheumatism Council (ARC) National Repository in Manchester, 65 multicase families from Cleveland, Ohio, USA, and 253 consecutive patients with RA attending clinics in Nottingham. Results-Mean ages of disease onset in the parents affected with RA were consistently greater than those in the probands. In the ARC data, the mean age difference in disease onset between the affected mother and proband pairs was 16.0 years (95% confidence interval (CI) 7.2 to 24.8 years, n = 11); in the Cleveland data it was 7.8 years (95% CI 0.9 to 14.7 years, n = 24), and in the Nottingham data it was 10.4 years (95% CI 2.8 to 18.0 years, n = 28). Similar results were found in the limited number of father-proband pairs. Unlike the findings of earlier work, there was no correlation between proband age at disease onset and age of the parent at conception of the proband. Conclusion-In independent and larger familial RA data sets, features of genetic anticipation were replicated. Our findings support the case for further research at a molecular level into genetic anticipation in those families with two successive generations affected by RA.