Genetic heterogeneitiy of Crigler-Najjar syndrome type I: A study of 14 cases

Philippe Labrune, Anne Myara, Michèle Hadchouel, Flavio Ronchi, Olivier Bernard, François Trivin, Namita Roy Chowdhury, Jayanta Roy Chowdhury, Arnold Munnich, Michel Odièvre

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Abstract

Crigler-Najjar syndrome type I (CN-I) is an autosomal recessive condition characterized by severe unconjugated hyperbilirubinemia caused by the lack of bilirubin-UDP-glucuronosyltransferase (B-UGT) activity in the liver. Two B-UGTs are coded for by a gene complex (UGT1) that maps to chromosome 2q37 and that also encodes two phenol-UDP-glucuronosyltransferases. Here, we report eleven mutations (including nine novel mutations) of the B-UGT1 gene in a large series of 14 unrelated CN-I children of various geographic origins: France (seven patients: A401P, Q357X, W335X, A368T, 1223insG, A291V, K426E, K437X); Portugal (two patients: G308E); Tunisia (two patients: Q357R); Turkey (one patient: S381R); Italy (two siblings: S381R). Interestingly, 6/14 mutant alleles carried by unrelated probands of French ancestry bore the A401P mutation, indicating a founder effect; this effect is probably also present in Portugal, Turkey, and Tunisia. Since mutations occurred in exons 2-5 shared by all mRNAs species of the gene, a combined deficiency of B-UGT and P-UGT was observed in the liver of five patients in whom these activities were measured. The present study confirms that CN-I is genetically heterogeneous and suggests that different founder effects are involved in Western Europe, the Middle East, and North Africa.

Original languageEnglish (US)
Pages (from-to)693-697
Number of pages5
JournalHuman Genetics
Volume94
Issue number6
DOIs
StatePublished - Dec 1 1994

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Labrune, P., Myara, A., Hadchouel, M., Ronchi, F., Bernard, O., Trivin, F., Roy Chowdhury, N., Roy Chowdhury, J., Munnich, A., & Odièvre, M. (1994). Genetic heterogeneitiy of Crigler-Najjar syndrome type I: A study of 14 cases. Human Genetics, 94(6), 693-697. https://doi.org/10.1007/BF00206965