title: Clinical features, outcomes, and genetic analysis in Korean children with Alagille syndrome.
abstract: 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 Korean children with AGS.
  
  
  METHODS
  Between January 1997 and December 2013, 19 children were diagnosed with AGS at Asan Medical Center, Seoul, Korea. 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.
  
  
  CONCLUSIONS
  This study describes the clinical characteristics of 19 Korean 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.
authors: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Jin Min
authors: JM
authors: Cho
authors: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Seak Hee
authors: SH
authors: Oh
authors: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Hyun Jin
authors: HJ
authors: Kim
authors: Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors: Joon Sung
authors: JS
authors: Kim
authors: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Kyung Mo
authors: KM
authors: Kim
authors: Genome Research Center for Genetic Disorders, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Gu-Hwan
authors: GH
authors: Kim
authors: Pathology, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Eunsil
authors: E
authors: Yu
authors: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.|Genome Research Center for Genetic Disorders, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Beom Hee
authors: BH
authors: Lee
authors: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.|Genome Research Center for Genetic Disorders, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Han-Wook
authors: HW
authors: Yoo
mesh_terms: D016738:Alagille Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D000072100:Jagged-1 Protein / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D051883:Receptor, Notch2 / Q000235:genetics* / Q000378:metabolism; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors
chemical_list: C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; C497764:NOTCH2 protein, human; D051883:Receptor, Notch2; D004247:DNA
keywords: Alagille syndrome; Jagged 1; Notch2 receptor; cholestasis; treatment outcome