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Case series
Ref Number: APCP-RP-116

Genetic Profiling of Progressive Familial Intrahepatic Cholestasis (PFIC); The First Report From Sri Lanka

Prranavethya Sivakumar¹, Meranthi Fernando², Priyanga Padmasiri³, Padmapani Padeniya⁴, Chamali Thanthiriwattha², Manissha Rajeindran⁵
1- University Paediatric Unit, Colombo North Teaching Hospital, Ragama, Sri Lanka 2- Colombo North Centre for Liver Diseases, University of Kelaniya, Sri Lanka 3- Colombo North Teaching Hospital, Sri Lanka 4- Department of Anatomy, Faculty of Medicine, University of Kelaniya, Sri Lanka 5- Credence Genomics Holdings Pte Ltd, Singapore
Corresponding Author: Prranavethya Sivakumar (prranavethya.sivakumar@gmail.com)
Abstract Body
Introduction: Progressive familial intrahepatic cholestasis (PFIC) comprises a group of autosomal recessive disorders affecting bile acid transport. Objective: We aimed to characterize the clinical and molecular spectrum of PFIC via genomic confirmation. Methods: A retrospective review was conducted on the PFIC database (2020–2025) maintained following consent, at the Colombo North Centre for Liver Diseases Sri Lanka. Data on demographics, clinical presentation, investigations, histology , and outcomes were analyzed. Whole-exome sequencing (WES) was performed and variant interpretation incorporated ClinVar, multiple in silico prediction tools (SIFT, PolyPhen-2, MutationTaster), population frequencies from gnomAD, and ACMG-AMP guidelines. Results: Of the 13 children with genetically confirmed PFIC, the median age was 19 months (range 7 months – 13 years). The majority were females (11/13;84.6%). PFIC3 was the most prevalent subtype (6/13; 46.1%), followed by PFIC2 (4/13; 30.7%), PFIC1 (2/13; 15.3%), and PFIC10 (1/13;7 .7%) corresponding to variants in ABCB4, ABCB11, ATP8B1 and MYO5B genes, respectively . Nine patients carried homozygous variants, while four had compound heterozygous variants. Of the variants detected, 2 were classified as pathogenic/likely pathogenic, while 10 were variants of uncertain significance (VUS). One homozygous missense variant was a novel mutation (ENST00000263817 .6) in the ABCB11 gene. The majority presented with decompensated chronic liver disease while one presented with acute liver failure. Histology revealed canalicular cholestasis with variable fibrosis and giant cell transformation. Conclusion: This review shows that PFIC is recognized as a cause of chronic cholestatic liver disease among children in Sri Lanka of which the diagnosis is now unveiled with the availability of WES.
Keywords: Familial intrahepatic cholestasis; Liver disease; Variants
Presentation Type: Case series
Disclaimer: The Views and opinions expressed in the articles are of the authors and not of the journal.
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