A Chinese girl molecularly diagnosed with Alagille syndrome.
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.


CONCLUSIONS
Genes in the Notch signaling pathway should be further studied in AGS, and used to confirm clinical or prenatal diagnosis and facilitate genetic counseling.
Li
Fu-Bang
FB
Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Chen
Jie
J
Yu
Jin-Dan
JD
Gao
Hui
H
Qi
Ming
M
D016738:Alagille Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D001706:Biopsy; D002135:Calcium-Binding Proteins / Q000235:genetics; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D000072099:Serrate-Jagged Proteins
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins