RESUMO
Mutations in the human gene Jagged1 (JAG1) localized in 20p12 have been recently identified as causal for the anomalies found in patients with Alagille syndrome (AGS). This gene encodes a ligand for the Notch1 transmembrane receptor, which plays a key role in cell-to-cell signaling during differentiation and is conserved from C. elegans to human. We report a paracentric inversion (PAI) of chromosome 20p12.2p13 in an individual with AGS who also had alpha-1-antitrypsin deficiency. To our knowledge, this is the first published case of PAI involving the short arm of chromosome 20. Using FISH, fiberFISH, and molecular studies with a approximately 40 kb cosmid clone encompassing the entire 36 kb JAG1 gene, we demonstrate that the gene was disrupted by the inversion breakpoint between exons 5 and 6. An unusual association between two most common causes of chronic liver disease in childhood, AGS and alpha-1-antitrypsin deficiency, as well as their influence on the proband's abnormal phenotype are discussed.
Assuntos
Síndrome de Alagille/genética , Inversão Cromossômica , Cromossomos Humanos Par 20/genética , Proteínas/genética , Síndrome de Alagille/patologia , Southern Blotting , Proteínas de Ligação ao Cálcio , Pré-Escolar , Bandeamento Cromossômico , DNA/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Peptídeos e Proteínas de Sinalização Intercelular , Proteína Jagged-1 , Masculino , Proteínas de Membrana , Mutação , Proteínas Serrate-JaggedRESUMO
The aim of the study was to assess the apolipoprotein E polymorphism (apoE) in two familial cholestatic diseases-Alagille syndrome (AS) and progressive familial intrahepatic cholestasis (PFIC)-and to estimate its association with gallstone formation, cholesterol levels, and response to UDCA treatment. We investigated 16 children with AS age 8.8 +/- 5.7 years (mean +/- SD) and 18 children with PFIC age 6.3 +/- 4.6 years. The frequency of the epsilon-2 allele in AS and PFIC was higher and the frequency of the epsilon-3 allele was lower than in controls. Gallstones were diagnosed in nine children with PFIC and different apoE phenotypes. No association between phenotype and cholesterol levels or response to UDCA therapy was observed in the patients studied. In conclusion, the allele epsilon-2 is overrepresented in AS and PFIC, similar to primary biliary cirrhosis, although this does not seem to contribute to different cholesterol levels, gallstones, and response to UDCA therapy.
Assuntos
Síndrome de Alagille/genética , Apolipoproteínas E/genética , Colagogos e Coleréticos/uso terapêutico , Colelitíase/genética , Colestase Intra-Hepática/genética , Colesterol/sangue , Ácido Ursodesoxicólico/uso terapêutico , Adolescente , Síndrome de Alagille/sangue , Síndrome de Alagille/tratamento farmacológico , Bilirrubina/sangue , Criança , Pré-Escolar , Colelitíase/sangue , Colelitíase/prevenção & controle , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/tratamento farmacológico , Feminino , Humanos , Masculino , Fenótipo , Polimorfismo Genético , Prurido/etiologia , Estudos RetrospectivosRESUMO
Aim of this study was to determine and further characterize the serum aminopeptidase-M in children with liver diseases. Based on our new assay, we have shown two fractions of the enzyme. Activity of the first fraction is expressed in undiluted serum at pH adjusted from 8.5 (pH of storaged serum) to 7.4. Activity of the second fraction (cryptic activity) appears in the serum (pH 7.4) as a result of dilution and/or addition of aniline naphthalene sulfonic acid. In children with Alagille syndrome, extrahepatic biliary duct atresia, Byler's disease, and acute hepatitis due to hepatitis B virus infection, activities of both fractions are highly elevated as compared to healthy children or those with chronic viral hepatitis. Moreover, serum aminopeptidase-M seems to reflect other aspects of the pathological process than those reflected by the alanine aminotransferase and gamma-glutamyltranspeptidase. Due to increased activity and broad substrate specificity, the enzyme seems to be also a cofactor of cholestasis and hepatitis.
Assuntos
Aminopeptidases/sangue , Antígenos CD13/sangue , Colestase/enzimologia , Hepatite B/enzimologia , Hepatopatias/enzimologia , Adolescente , Síndrome de Alagille/enzimologia , Atresia Biliar/enzimologia , Criança , Pré-Escolar , Colestase Intra-Hepática/enzimologia , Humanos , Concentração de Íons de Hidrogênio , LactenteRESUMO
Serum and salivary IgA and IgG antigliadin antibodies were determined by an enzyme-linked immunosorbent assay in 18 children with villous atrophy and 30 children on a gluten-free diet for coeliac disease in whom normal intestinal mucosa was found. Serum IgA anti-endomysium antibodies were also determined by an immunofluorescence method in these children. Serum IgG antigliadin and IgA anti-endomysium antibodies had the highest sensitivity (100 and 94.4%, respectively), followed by serum IgA antibodies to gliadin (72.2%), salivary IgA antigliadin (61.2%) and IgG antigliadin (50%) antibodies. The highest specificity was found for serum IgA anti-endomysium (100%) and IgA antigliadin (96.6%) antibodies and salivary IgA and IgG antigliadin antibodies (93.3%), while serum IgG antigliadin antibodies were found to be least specific (63.3%).