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Complement factor H deficiency and endocapillary glomerulonephritis due to paternal isodisomy and a novel factor H mutation.


Complement factor H (CFH) is a regulator of the alternative complement activation pathway. Mutations in the CFH gene are associated with atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II and C3 glomerulonephritis. Here, we report a 6-month-old CFH-deficient child presenting with endocapillary glomerulonephritis rather than membranoproliferative glomerulonephritis (MPGN) or C3 glomerulonephritis. Sequence analyses showed homozygosity for a novel CFH missense mutation (Pro139Ser) associated with severely decreased CFH plasma concentration (<6%) but normal mRNA splicing and expression. The father was heterozygous carrier of the mutation, but the mother was a non-carrier. Thus, a large deletion in the maternal CFH locus or uniparental isodisomy was suspected. Polymorphic markers across chromosome 1 showed homozygosity for the paternal allele in all markers and a lack of the maternal allele in six informative markers. This combined with a comparative genomic hybridization assay demonstrated paternal isodisomy. Uniparental isodisomy increases the risk of homozygous variations in other genes on the affected chromosome. Therefore, we analyzed other susceptibility genes on chromosome 1 and found no sequence variation in membrane cofactor protein, but homozygosity for the common deletion of CFH-related proteins 1 and 3, which may contribute to the early onset of disease.


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  • Authors+Show Affiliations


    Department of Clinical Immunology, Laboratory of Molecular Medicine, Rigshospitalet, Copenhagen, Denmark.

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    Genes and immunity 12:2 2011 Mar pg 90-9


    Antigens, CD46
    Blood Proteins
    Chromosomes, Human, Pair 1
    Complement C3b Inactivator Proteins
    Complement Factor H
    Complement Pathway, Alternative
    Gene Expression Regulation
    Genetic Variation
    Mutation, Missense
    RNA, Messenger
    Sequence Analysis, DNA
    Uniparental Disomy

    Pub Type(s)

    Case Reports
    Journal Article
    Research Support, Non-U.S. Gov't



    PubMed ID