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. 2025 Aug;108(2):206-211.
doi: 10.1111/cge.14728. Epub 2025 Feb 16.

Intrahepatic Cholestasis of Pregnancy: A Single-Centre Whole-Exome Sequencing Study in a Maltese Cohort

Dorianne Spiteri  1 , Laura Grech  2 , Charles Savona-Ventura  1 , Nikolai Paul Pace  1
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Intrahepatic Cholestasis of Pregnancy: A Single-Centre Whole-Exome Sequencing Study in a Maltese Cohort

Dorianne Spiteri et al. Clin Genet. 2025 Aug.

Abstract

Intrahepatic cholestasis of pregnancy (ICP) has a multifactorial pathophysiology involving genetic, endocrine, and environmental factors. It is associated with maternal distress and adverse foetal outcomes. The monogenic aetiology of ICP remains unexplored in the Maltese population. We apply whole exome sequencing in 20 unrelated index cases to assess the molecular spectrum of variants in genes linked to bile acid transport. We shortlisted five unique heterozygous variants. Three ABCB4 variants, including a novel likely pathogenic stop-gain variant were detected. Three genealogically unrelated cases carried an ABCB4 p.Asn510Ser variant, suggestive of a founder through shared haplotype analysis. This study provides preliminary insight into the monogenic aetiology of ICP from an unstudied population. It expands the spectrum of genetic variants associated with ICP and provides evidence for a founder effect in the Maltese population.

Keywords: ABCB4; cholestasis; exome sequencing; intrahepatic cholestasis of pregnancy.

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References

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