Chinese researchers identified many new mutations in the JAG1 and NOTCH2 genes that are causative of Alagille syndrome. They stated, “The JAG1 and NOTCH2 genes showed a wide array of mutations,” and they concluded that the genetic detection of these mutations can aid diagnosis. 

More than 90% of Alagille syndrome cases are caused by mutations in the JAG1 gene, with the rest resulting from mutations in the NOTCH2 gene.

In order to analyze the genetic mutations in patients with Alagille syndrome and improve diagnosis, a team of researchers at Xi’an Children’s Hospital in China conducted a retrospective study in 18 patients with Alagille syndrome who were admitted to their hospital between January 2016 and January 2020.

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The researchers collected information about the clinical characteristics, biochemical parameters, genetic mutations, and prognosis of the patients. They then genetically analyzed the patients using next-generation sequencing of genes related to liver disease or whole-exome sequencing. They also verified the presence of the causative mutation in the family members of the patients using Sanger sequencing. 

The results showed that the patients had 14 JAG1 mutations and 6 NOTCH2 mutations. Of these, 6 mutations in the JAG1 gene and 4 mutations in the NOTCH2 gene were novel. They were c.1213delA(p.T405Lfs*7), c.1270dupG(p.A424Gfs*5), c.1741dupG(p.A581Gfs*8), c.3045delC(p.I1016Ffs*20), c.2000-2A>C, and c.625C>A(p.H209N) associated with the JAG1 gene and c.6961dupG(p.A2321Gfs*79), c.518G>T(p.G173V), c.6157C>T(p.R2053C), and c.710G>A(p.R237Q) associated with the NOTCH2 gene. 

The researchers wrote, “The phenotypes of [Alagille syndrome patients] are diverse.” They added, “Genetic detection can help diagnosis.”

Since there is currently no cure for Alagille syndrome, a better understanding of the underlying genetic cause of the disease can help researchers develop new treatments.


Liu XG, Wei HJ, Liu P, et al. Clinical features and gene mutation analysis of patients with Alagille syndrome. Article in Chinese. Zhonghua Yi Xue Za Zhi. 2021;101(31):2454-2459. doi:10.3760/cma.j.cn112137-20210111-00082