Researchers identified 5 new pathogenic variants of the JAG1 gene causing Alagille syndrome, as published in the Egyptian Journal of Medical Human Genetics. This is the first study reporting such variants in an Egyptian cohort.

More than 90% of Alagille syndrome cases are caused by a mutation in the JAG1 gene, leading to a disruption in the Notch signaling pathway. More than 200 different mutations in the JAG1 gene have been identified so far in people with Alagille syndrome.

Here, a team of researchers led by Noha A. Yassin from the Faculty of Medicine Cairo University in Egypt analyzed the clinical spectrum of Alagille syndrome in an Egyptian cohort of patients by partially sequencing the JAG1 gene.

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Read more about the etiology of Alagille syndrome

The team analyzed a total of 17 patients with the disease who were diagnosed based on clinical features including cholestatic liver disease and facial dysmorphism affecting all of the patients, cardiac abnormalities affecting 88.2% of the patients, butterfly vertebrae affecting 64.7% of the patients, posterior embryotoxon seen in 35.2% of the patients, poor growth recorded in 41% of the patients, xanthomata seen in 11.8% of the patients, and hiatus hernia.

They conducted a molecular analysis of 10 selected JAG1 exons and identified 5 new mutations. Two of these were nonsense mutations, 1 was a splicing mutation, another was a frameshift insertion, and the last was a frameshift deletion.

In 2 of the patients, the mutations could not be detected in the parents. The researchers, therefore, concluded that they must be de novo mutations.

“In conclusion, this cohort is the first molecular study in [Alagille syndrome] within the Egyptian population,” the researchers wrote. “Further studies are planned to cover the rest of the gene exons in more patients.”


Khairat R, El-Karaksy H, El-Bassyouni HT, et al. Broadening the clinical spectrum of ALGS: an Egyptian cohort with five novel mutations in JAG1 gene. Egypt J Med Hum Genet. 2022;23(28). doi:10.1186/s43042-022-00241-9