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IgA nephropathy associated with a novel N-terminal mutation in factor H.

Schmitt, Roland LU ; Krmar, Rafael T; Kristoffersson, Ann-Charlotte LU ; Söderberg, Magnus and Karpman, Diana LU (2011) In European Journal of Pediatrics 170. p.107-110
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pediatrics
volume
170
pages
107 - 110
publisher
Springer
external identifiers
  • wos:000286339900014
  • pmid:20734203
  • scopus:79151483254
ISSN
1432-1076
DOI
10.1007/s00431-010-1279-3
language
English
LU publication?
yes
id
b92f4ded-da16-48ce-af72-f58c74a80cc4 (old id 1665062)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20734203?dopt=Abstract
date added to LUP
2010-09-03 11:16:48
date last changed
2017-10-01 04:56:12
@article{b92f4ded-da16-48ce-af72-f58c74a80cc4,
  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.},
  author       = {Schmitt, Roland and Krmar, Rafael T and Kristoffersson, Ann-Charlotte and Söderberg, Magnus and Karpman, Diana},
  issn         = {1432-1076},
  language     = {eng},
  pages        = {107--110},
  publisher    = {Springer},
  series       = {European Journal of Pediatrics},
  title        = {IgA nephropathy associated with a novel N-terminal mutation in factor H.},
  url          = {http://dx.doi.org/10.1007/s00431-010-1279-3},
  volume       = {170},
  year         = {2011},
}