Prime

Type your tag names separated by a space and hit enter

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

Abstract

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Clinical Immunology, Laboratory of Molecular Medicine, Rigshospitalet, Copenhagen, Denmark. l.schejbel@gmail.com

    , , , , ,

    Source

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

    MeSH

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

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    21270828