Three novel mutations in the JAG1 gene in Czech families with the Alagille syndrome

PROCHÁZKOVÁ, Dagmar, Romana BORSKÁ, Lenka FAJKUSOVÁ, Petra KONEČNÁ, Eliška HLOUŠKOVÁ a Jan PAPEŽ. Three novel mutations in the JAG1 gene in Czech families with the Alagille syndrome. In Annual Sympozium of the Society for the Study of Inborn Errors of Metabolism, Athens, Greece, 4-7 September 2018, in JIMD, vol 41, S1/s.34-35. 2018. ISSN 0141-8955. Dostupné z: https://dx.doi.org/10.1007/s10545-0232-x.

Základní údaje

• Originální název: Three novel mutations in the JAG1 gene in Czech families with the Alagille syndrome
• Autoři: PROCHÁZKOVÁ, Dagmar, Romana BORSKÁ, Lenka FAJKUSOVÁ, Petra KONEČNÁ, Eliška HLOUŠKOVÁ a Jan PAPEŽ.
• Vydání: Annual Sympozium of the Society for the Study of Inborn Errors of Metabolism, Athens, Greece, 4-7 September 2018, in JIMD, vol 41, S1/s.34-35, 2018.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Konferenční abstrakt
• Obor: 30219 Gastroenterology and hepatology
• Stát vydavatele: Řecko
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 4.287
• Organizační jednotka: Lékařská fakulta
• ISSN: 0141-8955
• Doi: http://dx.doi.org/10.1007/s10545-0232-x
• Klíčová slova česky: Alagille syndrome
• Klíčová slova anglicky: Alagille syndrome

Anotace

Background: To find the cause of infantile cholestatic jaundice is often difficult in clinical practice, especially after ruling out common problems. It may be found in disorders of bile acid synthesis or secretion, hereditary fructose intolerance, mitochondrial hepatopathy, progressive familial intrahepatic cholestasis (including Byler), as well as in conditions characterised by biliary hypoplasia, e.g. Alagille syndrome (ALGS). ALGS is a highly variable multisystem disorder inherited in an autosomal dominant pattern with incomplete penetration. The disorder is caused by mutations in the JAG1 gene, only rarely in the NOTCH2 gene, which gives rise to malformations in multiple organs. The basic symptom of ALGS is the reduced number of bile ducts (bile duct paucity) within the liver combined with 5 diagnostic signs: cholestasis, congenital heart defects (most frequently peripheral pulmonary stenosis), abnormalities of the skeleton (most often butterfly vertebrae), eye defects (usually embryotoxon posterior) and characteristic triangle-shaped facial appearance with a broad forehead, deeply-set eyes, hypertelorism, low-set ears and long onion-shaped nose. The diagnosis is confirmed if three of the 5 signs are present. Methods: molecular-genetic examination of genes JAG1 and NOTCH2 in four probands who complied with the diagnostic criteria of ALGS. Results: Mutations in the JAG1 gene were confirmed in all four probands. We identified three novel mutations: c.3189dupG, c. 2039delG and c.1913delG. Conclusions: The symptoms of ALGS are variable because no correlation exists between the genotype and phenotype.