Alagille syndrome (ALGS, OMIM #118450) is an autosomal dominant disorder that 
affects multiple organ systems including the liver, heart, eyes, vertebrae, and 
face. ALGS is caused by mutations in one of two genes in the Notch Signaling 
Pathway, Jagged1 (JAG1) or NOTCH2. In this study, analysis of 21 Vietnamese ALGS 
individuals led to the identification of 19 different mutations (18 JAG1 and 1 
NOTCH2), 17 of which are novel, including the third reported NOTCH2 mutation in 
Alagille Syndrome. The spectrum of JAG1 mutations in the Vietnamese patients is 
similar to that previously reported, including nine frameshift, three missense, 
two splice site, one nonsense, two whole gene, and one partial gene deletion. 
The missense mutations are all likely to be disease causing, as two are loss of 
cysteines (C22R and C78G) and the third creates a cryptic splice site in exon 9 
(G386R). No correlation between genotype and phenotype was observed. Assessment 
of clinical phenotype revealed that skeletal manifestations occur with a higher 
frequency than in previously reported Alagille cohorts. Facial features were 
difficult to assess and a Vietnamese pediatric gastroenterologist was only able 
to identify the facial phenotype in 61% of the cohort. To assess the agreement 
among North American dysmorphologists at detecting the presence of ALGS facial 
features in the Vietnamese patients, 37 clinical dysmorphologists evaluated a 
photographic panel of 20 Vietnamese children with and without ALGS. The 
dysmorphologists were unable to identify the individuals with ALGS in the 
majority of cases, suggesting that evaluation of facial features should not be 
used in the diagnosis of ALGS in this population. This is the first report of 
mutations and phenotypic spectrum of ALGS in a Vietnamese population.