title: Incomplete penetrance of CD46 mutation causing familial atypical hemolytic uremic syndrome.
abstract: BACKGROUND
  Hemolytic uremic syndrome (HUS) secondary to homozygous mutations in CD46 is uncommon. While heterozygous individuals may remain asymptomatic, homozygous mutations with severely depleted CD46 surface expression without disease manifestation is rare.
  
  
  METHODS
  We report on two siblings with features suggestive of hemolytic uremic syndrome. Estimation of CD46 expression by flow cytometry and gene sequencing were performed in members of this family.
  
  
  RESULTS
  Three siblings, two of whom were symptomatic, had markedly decreased (<10%) cell surface expression of CD46 and homozygous splice site mutation (IVS2 + 2 T > G) in the CD46 gene; the other 10-year-old sibling was asymptomatic. The illness was preceded by dengue shock syndrome in the index case. Both parents and two other siblings were heterozygous for this CD46 mutation.
  
  
  CONCLUSIONS
  Homozygous IVS2 + 2 T > G mutation in CD46 gene, similar to heterozygous mutation, may be clinically silent at least during childhood. The role of antecedent infections in triggering the disease requires further examination.
authors: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Divya
authors: D
authors: Bhatia
authors: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Priyanka
authors: P
authors: Khandelwal
authors: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Aditi
authors: A
authors: Sinha
authors: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Pankaj
authors: P
authors: Hari
authors: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors: Hae Il
authors: HI
authors: Cheong
authors: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India. arvindbagga@hotmail.com.
authors: Arvind
authors: A
authors: Bagga
mesh_terms: D065766:Atypical Hemolytic Uremic Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics*; D009154:Mutation; D019683:Penetrance; D017422:Sequence Analysis, DNA; D035781:Siblings
chemical_list: C497857:CD46 protein, human; D051916:Membrane Cofactor Protein
keywords: Atypical hemolytic uremic syndrome; Dengue; Membrane cofactor protein