title: IgA nephropathy associated with a novel N-terminal mutation in factor H.
abstract: Most patients with IgA nephropathy exhibit complement deposition in the glomerular mesangium. Certain cases of IgA nephropathy have been associated with reduced levels of complement factor H. A recent study could not demonstrate mutations at the C-terminal of factor H. We describe a novel heterozygous mutation in factor H, position A48S (nucleotide position 142 G > T, alanine > serine), detected in exon 2 of a 14-year-old girl with IgA nephropathy. The patient exhibited reduced levels of C3 and factor H, the latter suggesting that the mutation affected factor H secretion. The patient developed initial signs and symptoms of glomerulonephritis at the age of 9 years but presented again at the age of 14 years with weight gain, renal failure, nephrotic-range proteinuria and malignant hypertension. Blood tests suggested the development of microangiopathic hemolytic anemia (MAHA) but the renal biopsy was mostly indicative of chronic changes associated with IgA nephropathy as well as vascular changes associated with malignant hypertension. Immunofluorescence exhibited deposits of IgA, C3, and IgM. Screening of the factor H gene revealed, in addition to the mutation, three heterozygous hemolytic uremic syndrome -associated risk polymorphisms (-257 c/t, 2089 a/g, and 2881 g/t) which may have increased the patient's susceptibility to the occurrence of MAHA triggered by malignant hypertension. The combined clinical picture of IgA nephropathy and MAHA may have been partly related to the alterations in factor H.
authors: Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185 Lund, Sweden.
authors: Roland
authors: R
authors: Schmitt
authors: Rafael T
authors: RT
authors: Krmar
authors: Anncharlotte
authors: A
authors: Kristoffersson
authors: Magnus
authors: M
authors: Söderberg
authors: Diana
authors: D
authors: Karpman
mesh_terms: D000293:Adolescent; D017242:Complement Factor H / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D006974:Hypertension, Malignant / Q000209:etiology*; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000209:etiology
chemical_list: D017242:Complement Factor H