Clinical exome sequencing reveals a novel pathogenic variant in KIF12 underlying cholestasis with highly variable phenotypes

Abstract

Four affected individuals from a large consanguineous family were diagnosed with variable phenotypes of cholestasis based on their clinical laboratory and biopsy findings. Cholestasis is a condition when there is not enough bile flow between liver and small intestine. Two of the affected individuals (IV‐1, IV‐4) died of cholestatic liver at an early age, while the other two patients are alive with chronic liver disease. Clinical exome and Sanger sequencing identified a novel homozygous pathogenic variant (c.482‐7_500del) in the patients.

Youngest Living Donor Liver Transplant for End‐Stage Liver Disease in a 6‐Month‐Old With a Novel Aggressive Mutation in KIF12 Gene

“…The first report of KIF12 mutation causing high GGT genetic cholestasis was published in the year 2019 by two independent case series [5,6]. Following this discovery, other researchers have also reported similar cases of KIF12-associated pediatric cholestasis resulting in a total of 21 published cases in the last 3-4 years [7][8][9]. Recently from India also, two such patients have been reported from northern and southern regions in 2023 [10,11].…”

“…Patients with KIF12-associated intrahepatic cholestasis have been reported to have a highly heterogeneous clinical spectrum ranging from milder phenotypes to rapidly progressive liver fibrosis and cirrhosis even within the members of the same family [9]. Typically, they present in infancy or early childhood with jaundice, pruritus, and hepatomegaly which can progress later on to a decompensated liver disease state with ascites/coagulopathy.…”