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 1994

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Crigler-Najjar Syndrome
bilirubin glucuronoside glucuronosyltransferase
Founder Effect
Tunisia
Mutation
Portugal
Turkey
Genes
Northern Africa
Eastern Africa
Hyperbilirubinemia
Middle East
Liver
Italy
France
Siblings
Exons
Chromosomes
Alleles
Messenger RNA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Labrune, P., Myara, A., Hadchouel, M., Ronchi, F., Bernard, O., Trivin, F., ... 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

Genetic heterogeneitiy of Crigler-Najjar syndrome type I : A study of 14 cases. / Labrune, Philippe; Myara, Anne; Hadchouel, Michèle; Ronchi, Flavio; Bernard, Olivier; Trivin, François; Roy Chowdhury, Namita; Roy-Chowdhury, Jayanta; Munnich, Arnold; Odièvre, Michel.

In: Human Genetics, Vol. 94, No. 6, 12.1994, p. 693-697.

Research output: Contribution to journalArticle

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, vol. 94, no. 6, pp. 693-697. https://doi.org/10.1007/BF00206965
Labrune P, Myara A, Hadchouel M, Ronchi F, Bernard O, Trivin F et al. Genetic heterogeneitiy of Crigler-Najjar syndrome type I: A study of 14 cases. Human Genetics. 1994 Dec;94(6):693-697. https://doi.org/10.1007/BF00206965
Labrune, Philippe ; Myara, Anne ; Hadchouel, Michèle ; Ronchi, Flavio ; Bernard, Olivier ; Trivin, François ; Roy Chowdhury, Namita ; Roy-Chowdhury, Jayanta ; Munnich, Arnold ; Odièvre, Michel. / Genetic heterogeneitiy of Crigler-Najjar syndrome type I : A study of 14 cases. In: Human Genetics. 1994 ; Vol. 94, No. 6. pp. 693-697.
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