Author Affiliations: Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Li FB, Chen J, Yu JD); Center for Genetic & Genomic Medicine, Zhejiang University, Hangzhou 310058, China (Gao H, Qi M); Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA (Qi M)

Corresponding Author: Ming Qi, Center for Genetic & Genomic Medicine, Zhejiang University, Hangzhou 310058, China (Tel: +86-571-87061007; Fax: +86-571-87033296; Email: ming_qi@urmc.rochester.edu)

doi:10.1007/s12519-010-0226-8

Background: Alagille syndrome (AGS) is a rare or fatal disease affecting multiple systems including the liver, heart, eyes, skeleton and face. It has been considered a genetically heterogeneous disorder of the Notch signaling pathway.

Methods: A 28-month-old Chinese girl with congenital heart disease and jaundice was diagnosed with Alagille syndrome by liver biopsy showing a paucity of the intrahepatic bile ducts. Variants of the JAG1 gene were detected by DNA sequencing in the patient and her unaffected father.

Results: A heterozygous missense mutation was identified in exon 2 of the JAG1 gene in the proband but not in exon 2, 4, 6, 9, 17, 23, 24 by DNA sequencing in her father. The mutation G→T change was seen at position 133 in the cDNA sequence (c.133 G→T), causing a substitution of a leucine for a valine (V45L) residue in the N terminus between signal peptide and DSL domain of the Notch ligand. This mutation, however, was absent in her father.

Conclusion: Genes in the Notch signaling pathway should be further studied in AGS, and used to confirm clinical or prenatal diagnosis and facilitate genetic counseling.

Key words: Alagille syndrome; mutation; Notch2 receptor

World J Pediatr 2010;6(3):278-280