Novel ATP8B1 gene mutation in a family with progressive familial intrahepatic cholestasis

Area of Science:

• Genetics
• Hepatology
• Pediatric Gastroenterology

Background:

• Progressive familial intrahepatic cholestasis (PFIC) comprises rare, heterogeneous autosomal recessive hepatobiliary disorders.
• PFIC type 1 (PFIC 1) is linked to mutations in the ATP8B1 gene, typically presenting with infantile cholestasis, pruritus, malabsorption, and progressive liver failure.

Purpose of the Study:

• To report two siblings with diverse clinical manifestations of a fatal hepatic disease.
• To identify the genetic basis of PFIC 1 in these patients.

Main Methods:

• Clinical case presentation of two siblings.
• Carrier whole-exome sequencing of parental DNA.

Main Results:

• Both siblings presented with varying clinical features of a fatal hepatic disease.
• A novel heterozygous pathogenic mutation in exon 28 of the ATP8B1 gene was identified in both parents.

Conclusions:

• The identified novel ATP8B1 mutation validates the diagnosis of PFIC 1 in the affected siblings.
• This finding highlights the genetic heterogeneity and variable clinical expressivity of PFIC 1.