Mutations in () gene in Indian children with hemolytic uremic syndrome.

BACKGROUND

Mutations in the gene account for an important proportion of patients with atypical hemolytic uremic syndrome (aHUS) who characteristically show multiple relapses, no response to plasma exchange and low recurrence risk in allograft. We screened for mutations in in patients with and without circulating anti-factor H (FH) antibodies-associated aHUS.

METHODS

We estimated surface expression by flow cytometry and sequenced the gene in 23 and 56 patients with and without circulating anti-FH antibodies, respectively. Human Splicing Finder and PolyPhen2 were used for prediction of pathogenicity.

RESULTS

Two novel and three known (c.286 +2T > G, c.104G > A and c.565T > G) mutations in were found in nine (11.4%) patients; one patient had a variant of unknown significance and two patients presented during the first year of life. Novel intronic (c.1127 + 46C > G) and exonic (c.911C > T) mutations are proposed to activate cryptic splicing sites or alter protein conformation. Markedly reduced CD46 surface expression was found in homozygous states in five patients.

CONCLUSION

Patients with mutations in present at all ages, including the first year of life. Mutations in intron 2, (c.286 +2T > G) may be a potential hot spot in Indian children. Flow cytometry for CD46 expression is a satisfactory screening tool enabling early diagnosis.