Divya Bhatia1, Priyanka Khandelwal1, Aditi Sinha1, Pankaj Hari1, Hae Il Cheong2,3,4, Arvind Bagga5. 1. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India. 2. Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea. 3. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea. 4. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. 5. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India. arvindbagga@hotmail.com.
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.
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.
Entities:
Keywords:
Atypical hemolytic uremic syndrome; Dengue; Membrane cofactor protein
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