Atypical hemolytic uremic syndrome and mutation analysis of factor H gene in two Tunisian families

Abstract

Imen Habibi1,Imen Sfar1,Walid Ben Alaya1, Jihen Methlouthi2, Abdelkrim Ayadi2, Mounira Brahim2, Jacques Blouin3, Raoudha Dhagbouj1, Thouraya Ben Rhomdhane1, Mouna Makhlouf1, Houda Aouadi1, Saloua Ayed-Jendoubi1, Véronique Fremeaux-bacchi3, Tahar Sfar2, Taieb Ben Abdallah1, Khaled Ayed1, Yousr Gorgi11Laboratory of Immunology, Charles Nicolle Hospital, Tunis, Tunisia; 2Paediatric Department, Tahar Sfar Hospital, Mahdia, Tunisia; 3Immunology Department, George Pompidou Hospital, Paris, FranceAbstract: We carried out a protein and genetic investigation of the ¬factor H gene mutations within two families presenting with a diagnostic suspicion of atypical hemolytic uremic syndrome (aHUS). The results within the patients of the first family revealed a factor H-deficiency. Direct sequencing allowed the detection of a 4-nucleotide deletion in the factor H gene. This deletion was found as the homozygote form in the proband and as the heterozygote form in the parents. Protein and functional analyses of the complement system were normal in all members of the second family. However, the molecular investigation for the father showed the presence of an amino acid substitution in the FH gene. Unfortunately, his two affected children died without being investigated for mutations. The functional consequences of these abnormal proteins are still to be demonstrated.Keywords: atypical hemolytic uremic syndrome, complement, alternative pathway, factor H, deletion, nucleotide substitution