ISSN 2756-3855
International Journal of Urology and Nephrology Vol. 1 (2), pp. 022-025, October, 2013. © International Scholars Journals
Full Length Research Paper
Factor I mutation in Tunisian patient with atypical hemolytic uremic syndrome
Nadia Leban1, Sabra Aloui2, Dalel Touati2, Donia El Hayek1, Habib Skhiri2, Gerard Lefranc3, Abdellatif Achour4, Mezri Elmay2, Jemni Chibani1 and Amel Haj Khelil1
1Biochemistry and Molecular Biology Laboratory, Faculty of Pharmacy, Monastir, Tunisia.
2Department of Nephrology, Fattouma Bourguiba Universitary Hospital, Monastir, Tunisia.
3Institute of Human Genetics, CNRS and University of Montpellier-II, France.
4Department of Nephrology, Sahloul Universitary Hospital, Sousse, Tunisia
*Corresponding author. E-mail: [email protected]. Tel: (+216) 73 46 10 00. Fax: (+216) 73 46 18 30.
Accepted 5 August, 2013
Astract
Atypical hemolytic uremic syndrome or the Shiga toxin-producing Escherichia coli (STEC) negative hemolytic uremic syndrome (HUS) is a rare disorder typically classified as familial or sporadic. Recent literature has suggested that approximately 50% of patients have mutations in factor H (CFH), factor I (CFI), or membrane cofactor protein (encoded by CD46). Importantly, results of renal transplantation in patients with mutations in either CFH or CFI are dismal, with recurrent disease leading to graft loss in the majority of cases. In this study, a case was described of a patient who developed atypical hemolytic uremic syndrome waiting for a kidney graft. A patient suffering from aHUS and his family was screened for CFI, CFH and membrane cofactor protein (MCP) mutations. The sequencing results of CFH, CFI, and CD46 genes revealed that the patient was heterozygous for a missense mutation, a substitution of a proline residue for a leucine residue at amino acid 64 in CFI. However, the molecular investigation for the family showed the presence of the same mutation in the CFI gene in two members. In silico study demonstrate a functional consequence of this abnormal protein. This study reemphasizes the importance of screening patients with atypical hemolytic uremic syndrome for mutations in the CFI, CFH and MCP genes before renal transplantation and shows the challenges in the management of these patients.
Key words: Hemolytic uremic syndrome (Ahus), complement proteins, factor I mutation, transplantation, in silico.