JAG1 Mutation Spectrum and Origin in Chinese Children with Clinical Features of Alagille Syndrome

• DOI: 10.1371/journal.pone.0130355
• Publication Date: 2015-06-15T18:08:46Z
• Authors: Liting Li; Jibin Dong; Xiaohong Wang; Hongmei Guo; Huijun Wang; Jing Zhao; Yiling Qiu; Kuerbanjiang Abud...; Jianshe Wang
• Keywords: Alagille Syndrome; JAG1; Nonsense mutation

Alagille syndrome is an autosomal dominant disorder that results from defects in the Notch signaling pathway, which most frequently due to JAG1 mutations. This study investigated rate, spectrum, and origin of mutations 91 Chinese children presenting with at least two clinical features (cholestasis, heart murmur, skeletal abnormalities, ocular characteristic facial features, renal abnormalities). Direct sequencing and/or multiplex-ligation-dependent probe amplification were performed these patients, segregation analysis was using samples available parents. disease-causing detected 70/91 (76.9%) including 29/70 (41.4%) small deletions, 6/70 (8.6%) insertions, 16/70 (22.9%) nonsense mutations, 8/70 (11.4%) splice-site (9.4%) missense 5/70 (7.1%) gross deletions. Of detected, 45/62 (72.6%) novel, almost all unique, exception c.439C>T, c.439+1G>A, c.703C>T, c.1382_1383delAC, c.2698C>T, c.2990C>A, cases each; three exhibited entire gene A majority (69.2%) point frameshift could be by eleven exons (exons 3, 5, 6, 11, 14, 16, 18, 21, 23–25). The mutation detection rate 50.0% (10/20) atypical only presented or syndrome. Segregation revealed 81.1% (30/37) de novo. In conclusion, are present pediatric patients syndrome, concentrate on different other reports. Genetic important for diagnosis patients.