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Clinical and genetic characteristics of a large cohort of children with Alagille syndrome: identification of 57 new variants in the JAG1 gene

Journal of Human Genetics (2026)Cite this article

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Abstract

Alagille syndrome (ALGS) is an inherited multisystem disorder with a broad phenotypic spectrum and no apparent genotype-phenotype correlation. This study aimed to present the clinical and genetic characteristics of 115 patients diagnosed with ALGS in the Russian Federation between 2010 and 2023. The most common pathogenic variants identified in the study cohort were c.2122_2125delCAGT p.(Gln708Valfs*34) and c.439+1G>A. Two previously undescribed JAG1 variants, c.247C>T p.(Gln83Ter) and c.1188del p.(Phe396Leufs*16), were assessed in silico as likely pathogenic. Functional analysis of four JAG1 variants (c.439+1G>A, c.1120+5G>A, c.886+3A>G, and c.1156G>A) and one NOTCH2 variant (c.1264+5G>A) using a minigene splicing assay classified them as pathogenic splice-site variants.

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Acknowledgements

We would like to thank all the families for their participation and cooperation in this study. Their contributions were essential for advancing our understanding of Alagille syndrome.

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (the Federal Scientific-technical program for genetic technologies development for 2019–2030; agreement. № 075-15-2025-481).

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Authors and Affiliations

  1. Research Centre for Medical Genetics, Moscow, Russia

    Elena A. Gusarova, Natalia A. Semenova, Ekaterina Y. Nuzhnaya, Eleonora A. Annenkova, Victoria Y. Bezverbnaya, Yana D. Nazarenko, Andrey V. Marakhonov & Ekaterina Y. Zakharova

  2. National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Moscow, Russia

    Anna V. Degtyareva, Marina S. Gautier, Elena A. Filippova, Ekaterina S. Shubina & Medan K. Isaeva

  3. Sechenov University, Moscow, Russia

    Anna V. Degtyareva

  4. Institute of Pediatrics of the University Clinic, Privolzhsky Research Medical University, Nizhny Novgorod, Russia

    Alla E. Lavrova, Ekaterina Y. Konovalova & Elena Y. Borisova

  5. Federal Research Centre of Nutrition and Biotechnology, Moscow, Russia

    Tatiana V. Strokova

Authors
  1. Elena A. Gusarova
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  2. Anna V. Degtyareva
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  9. Ekaterina S. Shubina
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  15. Elena Y. Borisova
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  16. Andrey V. Marakhonov
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  17. Ekaterina Y. Zakharova
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Contributions

Conceptualization: Elena A. Gusarova Methodology: Anna V Degtyareva, Alla E. Lavrova, Tatiana V. Strokova, Natalia A. Semenova and Ekaterina Y. Zakharova Data curation: Anna V Degtyareva, Alla E. Lavrova, Tatiana V. Strokova, Natalia A. Semenova, Ekaterina Y. Nuzhnaya, Marina S. Gautier, Elena A. Filippova, Medan K. Isaeva, Ekaterina Y. Konovalova and Elena Y. Borisova Formal analysis: Elena A. Gusarova, Ekaterina S. Shubina and Andrey V. Marakhonov Investigation: Elena A. Gusarova, Eleonora A. Annenkova and Victoria Y. Bezverbnaya Writing (original draft): Elena A. Gusarova, Yana D. Nazarenko and Victoria Y. Bezverbnaya Writing (review and editing): Ekaterina Y. Zakharova, Anna V Degtyareva, Alla E. Lavrova and Natalia A. Semenova Visualization: Elena A. Gusarova and Eleonora A. Annenkova Supervision: Ekaterina Y. Zakharova.

Corresponding author

Correspondence to Elena A. Gusarova.

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Gusarova, E.A., Degtyareva, A.V., Lavrova, A.E. et al. Clinical and genetic characteristics of a large cohort of children with Alagille syndrome: identification of 57 new variants in the JAG1 gene. J Hum Genet (2026). https://doi.org/10.1038/s10038-026-01462-1

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