Genetic studies into inherited and sporadic hemolytic uremic syndrome

Kidney Int. 1998 Apr;53(4):836-44. doi: 10.1111/j.1523-1755.1998.00824.x.


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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Complement Factor H / genetics
  • Complement System Proteins / metabolism*
  • DNA Mutational Analysis
  • DNA, Satellite / genetics
  • DNA, Satellite / isolation & purification
  • Female
  • Frameshift Mutation*
  • Genetic Linkage
  • Genotype
  • Hemolytic-Uremic Syndrome / genetics*
  • Hemolytic-Uremic Syndrome / metabolism*
  • Humans
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • RNA, Messenger / analysis
  • RNA, Messenger / isolation & purification


  • CFH protein, human
  • DNA, Satellite
  • RNA, Messenger
  • Complement Factor H
  • Complement System Proteins