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

Abstract

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.

• Authors: 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
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 62 Issue 5 Pg. 978-83 (Nov 2013) ISSN: 1523-6838 [Electronic] United States
• PMID: 23870792 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Membrane Cofactor Protein
• Complement Factor H

Topics

• Atypical Hemolytic Uremic Syndrome
• Complement Factor H (deficiency, genetics)
• Genotype
• Haplotypes (genetics)
• Hemolytic-Uremic Syndrome (genetics)
• Hereditary Complement Deficiency Diseases
• Homozygote
• Humans
• Infant
• Kidney Diseases (genetics)
• Male
• Membrane Cofactor Protein (genetics)
• Mutation (genetics)
• Phenotype
• Polymorphism, Single Nucleotide (genetics)
• Uniparental Disomy (genetics)