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From the Multiple Sclerosis Center (Drs. M. Marrosu, Lai, Cocco, Loi, Spinicci, Pischedda, Massole, and G. Marrosu), Department of Neuroscience, Ospedale Binaghi, Cagliari, Italy; and Department of Public Health (Dr. Contu), University of Cagliari, Italy.
Address correspondence and reprint requests to Dr. M. Marrosu, Centro Sclerosi Multipla, Ospedale Binaghi, Via Is Guadazzonis, 2, 09126 Cagliari, Italy; e-mail: gmarrosu{at}unica.it
Objective: To estimate the presence of familial aggregation and determine the contribution of genetic factors to familial clustering of MS in patients coming from Sardinia, a Mediterranean island considered a genetically homogeneous, isolated area having high disease incidence and prevalence.
Methods: Recurrence risk in siblings of 901 Sardinian patients and factors influencing risk (patient and sibling sex, patient age at onset, sibling birth cohort, and presence of affected relatives other than siblings) were examined. The presence of distant familial relationships among patients was evaluated by tracing the extended pedigrees of all patients with MS born in one Sardinian village.
Results: Twenty-three brothers and 36 sisters of the 2,971 siblings were affected with MS. Recurrence risk was greater in siblings of index patients with onset age less than 30 years (p < 0.01, increased risk 2.33 times) and having a relative with MS other than a sibling or parent (p < 0.01, increased risk 2.90 times). Pedigree analysis of patients from the village of L. showed that all 11 patients descended from 3 pairs of ancestors, whereas no cases occurred in the remaining 2,346 inhabitants. In descendants from the 3 couples, MS prevalence was dramatically greater than the regional average and 1.5 times greater than that observed in siblings of affected cases.
Conclusions: Data from this study indicate that MS familial aggregation in Sardinians is influenced by genetic factors and that founder effect and the isolation of Sardinia can be considered causes of the enrichment of "etiologic" MS genes.
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