Genotype/phenotype correlations in complement factor h deficiency arising from uniparental isodisomy

Valerie Wilson, Rebecca Darlay, William Wong, Katrina M Wood, Jeannette McFarlane, Lone Schejbel, Ida M Schmidt, Claire L Harris, James Tellez, Eva-Maria Hunze, Kevin Marchbank, Judith A Goodship, Timothy H J Goodship

7 Citationer (Scopus)


We report a male infant who presented at 8 months of age with atypical hemolytic uremic syndrome (aHUS) responsive to plasma therapy. Investigation showed him to have complement factor H (CFH) deficiency associated with a homozygous CFH mutation (c.2880delT [p.Phe960fs]). Mutation screening of the child's parents revealed that the father was heterozygous for this change but that it was not present in his mother. Chromosome 1 uniparental isodisomy of paternal origin was confirmed by genotyping chromosome 1 SNPs. CD46 SNP genotyping was undertaken in this individual and another patient with CFH deficiency associated with chromosome 1 uniparental isodisomy. This showed a homozygous aHUS risk haplotype (CD46GGAAC) in the patient with aHUS and a homozygous glomerulonephritis risk haplotype (CD46AAGGT) in the patient with endocapillary glomerulonephritis. We also showed that FHL-1 (factor H-like protein 1) was present in the patient with aHUS and absent in the patient with glomerulonephritis. This study emphasizes that modifiers such as CD46 and FHL-1 may determine the kidney phenotype of patients who present with homozygous CFH deficiency.
TidsskriftAmerican journal of kidney diseases : the official journal of the National Kidney Foundation
Udgave nummer5
Sider (fra-til)978-83
Antal sider6
StatusUdgivet - nov. 2013


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