Table 3.

Complement pathogenic rare variants (n=6) found in six out of 108 patients with postdiarrheal HUS

PatientGeneVariantGenetic StatusNo. of PatientsCFH Plasma LevelaMCP ExpressionaMAFb (%)Demonstrated Functional AlterationsPreviously Reported in STEC-HUSPreviously Reported in aHUS
Stx-positive patients with HUS
 1Complement factor Hc.2850G>T p.Gln950HisHe1NormalNormal0.36Moderately decreased binding to GAG and/or C3b (Hemolytic assay) (35)Yes (24)Yesc (38)
 2Thrombomodulinc.1483C>T p.Pro495SerHe1NormalNormal0.06Decreased capacity to inactivate C3b (36)NoYes (36)
 3Complement factor Hc.1145C>A p.Ala382GluHe1LowNormalNot foundDecrease FH level associated with C3 consumption (CFH deficiency)dNoNo
 4Membrane cofactor proteinc.503_504insA p.Asn170LysfsTer7He1NormalLowNot foundDecrease MCP expression (MCP deficiency)dNoNo
Stx-negative patients with HUS
 5Thrombomodulinc.127G>A p.Ala43ThrHe1NormalNormal0.34Decreased capacity to inactivate C3b (36)NoYes (36)
 6Complement factor Hc.3628C>T p.Arg1210CyseHe1NormalNormal0.017Alter the C3b/polyanions–binding site (37)NoYesc (38)
  • HUS, hemolytic uremic syndrome; CFH, complement factor H; MCP, membrane cofactor protein; MAF, minor allele frequency; STEC, Shiga toxin producing E. coli; aHUS, atypical hemolytic uremic syndrome; He, heterozygous; GAG, glycosaminoglycans; FH, factor H.

  • a At discharge.

  • b MAF in Exome Aggregation Consortium database (http://exac.broadinstitute.org/).

  • c FH aHUS mutation database (http://www.fh-hus.org/).

  • d V.F.-B., personal communication.

  • e Patient 6 with CFH p.Arg1210Cys pathogenic rare variant also carried a C3 variant of uncertain significance.