Progressive familial intrahepatic cholestasis was a group of autosomal recessive intrahepatic cholestatic illnesses expanding. Recently, next-generation sequencing has made it possible to find new genes responsible for new diseases. About 2 biochemical phenotypes have been discovered according to gamma-glutamyltransferase (GGT) activity. It was known that mutations of the myosin 5B gene (MYO5B) cause microvillus inclusion disorder. About 32 children with cryptogenic intrahepatic cholestasis were the subjects of a multicenter retrospective and prospective investigation. In these individuals, clinical, biochemical, histological, and therapeutic data were evaluated. All patients were examined using whole-exome sequencing followed by Sanger sequencing using DNA taken from their peripheral blood. Around 6 out of 32 patients exhibited mutations in the MYO5B gene. The median age at disease onset for these 6 individuals was 0.8 years, and the median length of follow-up was 4.2 years. The most prevalent symptoms were pruritus, poor growth, hepatomegaly, jaundice, and hypocholic stools.

Additionally, 2 patients exhibited intestinal involvement. Serum bile acids were raised, serum transaminases and conjugated bilirubin were elevated, and GGT was persistently normal. Anti-Myo5B immunostaining revealed coarse granules within the cytoplasm of hepatocytes in the liver biopsies of 2 patients, although the bile salt export pump was typically expressed at the canalicular membrane. About 3 of the 6 variations in homozygosity or compound heterozygosity in the MYO5B gene have never been described previously. Except for a missense mutation discovered in the isoleucine-glutamine calmodulin-binding motif, all nucleotide modifications were found in the myosin motor domain. Researchers detected causal mutations in MYO5B in 18.7% of patients with intrahepatic cholestasis, establishing a function for the MYO5B gene in low-GGT cholestasis.