Sindrome di di Crigler-Najjar tipo 2: due nuove mutazioni missense nel gene UGT1A1.

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    Abstract

    [automatically translated] Crigler-Najjar syndrome (CNS) is a very rare disease (prevalence 1 / 1,000,000 births) autosomal recessive, characterized by a chronic and severe increase of serum bilirubin indirect (unconjugated), due to partial (type 2 ) or complete (type 1) liver enzyme functional absence glucoronosil transferase UGT1. The disease occurs in newborn babies with an early and intense jaundice due to unconjugated and physical examination presence of bilirubin is normal; in the development of age the clinical effects of CNS type 1 are lethal because the excess bilirubin encephalopathy inevitably leads to a being such highly fat-soluble pigment. The mutations described today to cause the absence of enzymatic synthesis or the synthesis of a non-functional aberrant product. The CNS type 2, in particular, is characterized by the presence of residual enzyme activity and is caused by mutations is autosomal dominant, with incomplete penetrance, which recessive in the UGT1A1 gene. The clinical trial of phenobarbital used to distinguish the two forms (type I and type II) while the genetic test is the most specific method for diagnosis. The UGT1A1 gene is located in the telomeric position on chromosome 2 (2q37.1) and extends to 110Kb. The gene consists of 4 consecutive exons (ex2-ex5) and by a group of 10 variants of exon 1 places the 5 'end. The selection for alternative splicing of exon 1 is finely regulated by the promoter and is responsible for the synthesis of the various isoforms of the enzyme (Fig. 1). The enzyme protein (precursor UDP-glucuronosyltransferase 1-1) consists of 533 amino acids. Missense mutations that correlate with the disease are about 79 and this number is constantly updated at the international database (website http://www.hgmd.cf.ac.uk/ac/index.php). Here we present two cases of Crigler Najjar type II due to two new mutations in the UGT1A1 gene and we emphasize that the genomic heterogeneity in our territory suggests a complete assessment of the UGT1A1 gene for a correct diagnosis of Crigler Najjar and a functional assessment of new mutations that were found.
    Original languageItalian
    Pages41-41
    Number of pages1
    Publication statusPublished - 2009

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