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

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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.

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Authors and Affiliations

  1. Unité de Recherche sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital des Enfants Malades, 75015, Paris, France

    Philippe Labrune & Arnold Munnich

  2. Service de Pédiatrie, Hôpital Antoine Béclère, 157 Rue de la Porte de Trivaux, 92141, Clamart Cedex, France

    Philippe Labrune & Michel Odièvre

  3. Laboratoire de Biochimie, Hôpital Saint Joseph, 75015, Paris, France

    Anne Myara & François Trivin

  4. INSERM U347, 94275, Le Kremlin Bicêtre Cedex, France

    Michèle Hadchouel & Olivier Bernard

  5. Ospedale Civile, Cattolica, Italy

    Flavio Ronchi

  6. Marion Bessin Liver Research Center and Department of Medicine, Albert Einstein College of Medicine, 10461, Bronx, NY, USA

    Namita Roy Chowdhury & Jayanta Roy Chowdhury

Authors
  1. Philippe Labrune
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  2. Anne Myara
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  3. Michèle Hadchouel
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  4. Flavio Ronchi
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  5. Olivier Bernard
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  6. François Trivin
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  7. Namita Roy Chowdhury
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  8. Jayanta Roy Chowdhury
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  9. Arnold Munnich
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  10. Michel Odièvre
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Additional information

These results were presented in part at the American Association for the Study of Liver Diseases, Chicago, November 4–7, 1993

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Labrune, P., Myara, A., Hadchouel, M. et al. Genetic heterogeneitiy of Crigler-Najjar syndrome type I: A study of 14 cases. Hum Genet 94, 693–697 (1994). https://doi.org/10.1007/BF00206965

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  • DOI: https://doi.org/10.1007/BF00206965

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