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- Title
Genetic studies into inherited and sporadic hemolytic uremic syndrome.
- Authors
Warwicker, P; Goodship, T H; Donne, R L; Pirson, Y; Nicholls, A; Ward, R M; Turnpenny, P; Goodship, J A
- Abstract
Hemolytic uremic syndrome (HUS) in adults carries a high morbidity and mortality, and its cause remains unknown despite many theories. Although familial HUS is rare, it affords a unique opportunity to elucidate underlying mechanisms that may have relevance to acquired HUS. We have undertaken a genetic linkage study based on a candidate gene approach. A common area bounded by the markers D1S212 and D1S306, a distance of 26 cM located at 1q32 segregated with the disease (Z max 3.94). We demonstrate that the gene for factor H lies within the region. Subsequent mutation analysis of the factor H gene has revealed two mutations in patients with HUS. In an individual with the sporadic/relapsing form of the disease we have found a mutation comprising a deletion, subsequent frame shift and premature stop codon leading to half normal levels of serum factor H. In one of the three families there is a point mutation in exon 20 causing an arginine to glycine change, which is likely to alter structure and hence function of the factor H protein. Factor H is a major plasma protein that plays a critical regulatory role in the alternative pathway of complement activation. In light of these findings and previous reports of HUS in patients with factor H deficiency, we postulate that abnormalities of factor H may be involved in the etiology of HUS.
- Publication
Kidney international, 1998, Vol 53, Issue 4, p836
- ISSN
0085-2538
- Publication type
Journal Article
- DOI
10.1111/j.1523-1755.1998.00824.x