Alternative titles; symbols
ORPHA: 2134, 544472;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20p11.21 | {Hemolytic uremic syndrome, atypical, susceptibility to, 6} | 612926 | Autosomal dominant | 3 | THBD | 188040 |
A number sign (#) is used with this entry because susceptibility to the development of atypical hemolytic uremic syndrome-6 (AHUS6) can be conferred by mutation in the gene encoding thrombomodulin (THBD; 188040).
Atypical hemolytic uremic syndrome-6 (AHUS6) consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, in the absence of a triggering Shiga toxin-producing E. coli infection (summary by Delvaeye et al., 2009).
For a general phenotypic description and a discussion of genetic heterogeneity of aHUS, see AHUS1 (235400).
Delvaeye et al. (2009) reported 7 patients with atypical hemolytic uremic syndrome characterized by 1 or more episodes of microangiopathic hemolytic anemia and thrombocytopenia associated with acute renal failure. Four patients had decreased serum C3 (120700), consistent with activation of the alternative complement pathway. C4 (120810) levels were normal.
In 7 (4.6%) of 153 patients with aHUS, Delvaeye et al. (2009) identified 6 different heterozygous mutations in the THBD gene (see, e.g., 188040.0005-188040.0008). In vitro functional expression studies showed that cells transfected with mutant THBD were less effective in converting C3b to iC3b on the cell surface after complement activation, and were thus not as well protected against complement activation. The findings indicated that mutations in the THBD gene contribute to the development of aHUS.
Delvaeye, M., Noris, M., De Vriese, A., Esmon, C. T., Esmon, N. L., Ferrell, G., Del-Favero, J., Plaisance, S., Claes, B., Lambrechts, D., Zoja, C., Remuzzi, G., Conway, E. M. Thrombomodulin mutations in atypical hemolytic-uremic syndrome. New Eng. J. Med. 361: 345-357, 2009. [PubMed: 19625716] [Full Text: https://doi.org/10.1056/NEJMoa0810739]