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Clinical features, outcomes, and genetic analysis in K orean children with A lagille syndrome
Author(s) -
Cho Jin Min,
Oh Seak Hee,
Kim Hyun Jin,
Kim Joon Sung,
Kim Kyung Mo,
Kim GuHwan,
Yu Eunsil,
Lee Beom Hee,
Yoo HanWook
Publication year - 2015
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.12602
Subject(s) - jag1 , medicine , alagille syndrome , missense mutation , cholestasis , gastroenterology , liver transplantation , heart failure , mutation , nonsense mutation , transplantation , genetics , gene , notch signaling pathway , receptor , biology
Background Alagille syndrome ( AGS ) is a multisystem autosomal dominant disorder that affects the liver, heart, eyes, face, bone, and other organs. AGS is caused by mutations in one of two genes, JAG1 or NOTCH2 . We evaluated clinical features, outcomes, and the presence of JAG1 and NOTCH2 mutations in K orean children with AGS . Methods Between J anuary 1997 and D ecember 2013, 19 children were diagnosed with AGS at A san M edical C enter, S eoul, K orea. Their clinical features, outcomes, and JAG1 and NOTCH2 mutation status were retrospectively analyzed. Results The prevalence of clinical features in the 19 patients was as follows: dysmorphic facial features, 100% ( n = 19); liver symptoms, 89% ( n = 17); cardiac symptoms, 95% ( n = 18); ophthalmologic symptoms, 67% ( n = 10); skeletal deformities, 47% ( n = 9); and renal symptoms, 21% ( n = 4). JAG1 mutations were identified in 14 patients. The 13 different JAG1 mutations, seven of which were novel, included four deletions, three insertions, two missense mutations, three nonsense mutations, and one indel mutation. No NOTCH2 mutations were found. Two patients who received liver transplantation due to liver failure were still alive. Two patients died of comorbidities related to AGS : one of cardiac failure and one of hepatic failure. Conclusion This study describes the clinical characteristics of 19 K orean AGS patients with seven novel JAG1 mutations. Neonatal cholestatic jaundice was the most common initial presenting symptom; thus the presence of neonatal cholestasis warrants screening for syndromic features of AGS . Complex heart anomalies and progressive liver dysfunction resulted in significant morbidity and mortality in AGS .