Phenotype-Genotype Correlation of North Indian Progressive Familial Intrahepatic Cholestasis type2 Children Shows p.Val444Ala and p.Asn591Ser Variants and Retained BSEP Expression

Abstract

Backgrounds and Aims: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by a defect or deficiency of bile salt export protein (BSEP) due to mutation in the ABCB11 gene. We intend to evaluate the phenotype–genotype correlation in 10 diagnosed cases of PFIC2 in a single tertiary care center in North India. Methods: The clinical, biochemical, histopathological, immunohistochemical, ultrastructural and genetic data of the 10 diagnosed cases of PFIC2 were recorded. Results: Icterus, pruritus and bleeding manifestations were the commonest clinical symptoms. Giant cell transformation was seen in 50% of the patients. Two predominant genetic variants were ABCB11 missense p.Val444Ala (c. 1331 T > C) and ABCB11 missense p.Asn591Ser (c. 1772 A > G) in their homozygous or compound heterozygous states and were associated with retained BSEP immunopositivity and reduced but retained BSEP immunopositivity respectively. Conclusion: Retention of BSEP is common in North Indian children of PFIC2 with no phenotype-genotype correlation.

Acknowledgement

The authors acknowledge the help of Drs Maesha Deheragoda, Rosa Miquel and Mrs Anne Rayner, Institute of Liver Studies, King’s College Hospital, London for their help in standardizing the BSEP immunostain. The authors also thank Professor Amanjit Bal, Drs. Vaishali Aggarwal and Ashwani Kumar Verma, PGIMER, Chandigarh for her help with the molecular genetics. The authors thank Mrs Kusum L. Chopra for her statistical help. The help of Dr. Charan Singh Rayat, technician-in-charge of electron microscopy and Mr Gurpreet Singh, technician-in-charge of immunohistochemistry laboratory, PGIMER, Chandigarh is also acknowledged.

Conflicts of interest

The authors disclose no conflicts of interest.

Additional information

Funding

The authors have received intramural grant from the Medical Education and Research Cell, PGIMER, Chandigarh (Grant No: 71/2-Edu-16/4834).