AbstractProgressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive disorders of childhood which presents with intermittent or progressive episodes of cholestasis, with jaundice and pruritus as most common presenting symptoms. PFIC type 3 occurs due to mutations in the ABCB4 gene, mutation in this gene has wide spectrum of features which include intrahepatic stones, cholelithiasis, PFIC type 3, and intrahepatic cholestasis of pregnancy. Here, we are reporting a peculiar case of young male adolescent with novel variant compound heterozygote missense mutation in ABCB4 gene who had gall stone as initial symptom, followed by symptoms of PFIC and eventually decompensated chronic liver disease.
Leptin and its receptor are essential for regulating food intake, energy expenditure, glucose homeostasis and fertility. Mutations within leptin or the leptin receptor cause early-onset obesity and hyperphagia, as described in human and animal models. The effect of both heterozygous and homozygous variants is much more investigated than compound heterozygous ones. Recently, we discovered a spontaneous compound heterozygous mutation within the leptin receptor, resulting in a considerably more obese phenotype than described for the homozygous leptin receptor deficient mice. Accordingly, we focus on compound heterozygous mutations of the leptin receptor and their effects on health, as well as possible therapy options in human and animal models in this review.
A Novel Compound Heterozygous Mutation in ABCB4 Gene Leading to Cholelithiasis, Progressive Familial Intrahepatic Cholestasis (Type 3), and Cirrhosis in a Child
