RT Journal Article SR Electronic T1 Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 676 OP 681 DO 10.1136/jmg.40.9.676 VO 40 IS 9 A1 H P H Neumann A1 M Salzmann A1 B Bohnert-Iwan A1 T Mannuelian A1 C Skerka A1 D Lenk A1 B U Bender A1 M Cybulla A1 P Riegler A1 A Königsrainer A1 U Neyer A1 A Bock A1 U Widmer A1 D A Male A1 G Franke A1 P F Zipfel YR 2003 UL http://jmg.bmj.com/content/40/9/676.abstract AB Background: The aetiology of atypical haemolytic uraemic syndrome (aHUS) is, in contrast to classical, Shiga-like toxin induced HUS in children, largely unknown. Deficiency of human complement factor H and familial occurrence led to identification of the factor H gene (FH1) as the susceptibility gene, but the frequency and relevance of FH1 mutations are unknown. Methods: We established a German registry for aHUS and analysed in all patients and 100 controls the complete FH1 gene by single strand confirmational polymorphism and DNA sequencing. In addition, complement C3 and factor H serum levels were assayed. Demographic data at onset of aHUS and follow up were compared for the mutation positive and negative groups. Results: Of 111 patients with aHUS (68 female, 43 male, mean age 33 years) 14% had FH1 germline mutations, including two of eight patients with familial aHUS.For each of these eight patients, both parents were tested, and we were able to trace the mutation for five cases. In the other three cases (one with the mutation 3749 C/T, one with 3200 T/C, and one with 3566+1 G/A), we could not detect the mutation in either parent, although paternity was proven by genetic fingerprinting, suggesting that these subjects have new mutations. C3 was decreased in five mutation carriers but also in two non-carriers, and factor H was decreased in none of the carriers, but elevated in six carriers and 15 non-carriers. Clinical parameters including associated medications and diseases, and outcome of aHUS and of post-aHUS kidney transplantation were similar in the mutation positive and negative groups. Conclusion:FH1 germline mutations occur with considerable frequency in patients with aHUS. Hypocomplementaemia is not regularly associated with a germline mutation, and factor H serum levels can even be elevated. Screening for FH1 mutations contributes to the classification of aHUS.