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A linkage study in two families with multiple sclerosis and healthy members with oligoclonal CSF immunopathy

Institute of Clinical Neuroscience, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden, sara.haghighi{at}neuro.gu.se

O Andersen

Institute of Clinical Neuroscience, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

S Nilsson

Institute of Mathematical Statistics, The Sahlgrenska Academy at Göteborg University, Sweden

L Rydberg

Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

J Wahlström

Department of Clinical Genetics, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

We studied two extended families in which not only multiple sclerosis (MS) segregates, but also approximately 18% of the cerebrospinal fluid (CSF) investigated blood relatives have ‘MS immunopathic trait’, an oligoclonal CSF immunopathy similar to that seen in MS, but with no neurological symptoms. Both families fit a genetic model for autosomal dominant inheritance for MS immunopathic trait, although with reduced penetrance in family A. In order to identify genetic factors of importance for the development of MS immunopathic trait, we performed a genome scan using the CHLC/Weber Screening Set (ver 6A), with 285 successful markers, to test the hypothesis that a single gene is causing the MS immunopathic trait in these families. Using a parametric method, we identified regions with suggestive linkage at chromosome 6q12 with a LOD-score of 2.4, putative linkage with LOD-score 1.5 at chromosome 6p21 (HLA region), putative linkage at chromosome 12q24 with a LOD-score of 1.7 and suggestive linkage at chromosome 19q13.2 with a LOD-score of 1.8. The LOD-score at chromosome 19q13.2 increased to 2.2 when only family A was analysed. In family A, all MS patients and two of five individuals with MS immunopathic trait had HLA DRB1*(15) and in family B, all blood relatives had the rare HLA type DRB1*0103, which is associated with other autoimmune diseases. We suggest that DRB1*0103 is a necessary but not sufficient condition for the susceptibility for MS immunopathic trait in this family.

Key Words: genome scan • healthy family members • linkage study • multiple sclerosis • quantitative trait

Multiple Sclerosis, Vol. 12, No. 6, 723-730 (2006)
DOI: 10.1177/1352458506070972


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