A growing category of autosomal recessive intrahepatic cholestasis illnesses is progressive familial intrahepatic cholestasis. Next-generation sequencing has recently enabled the identification of novel genes responsible for new particular illnesses. According to gamma-glutamyltransferase (GGT) activity, two biochemical phenotypes have been discovered. Microvillus inclusion disease is known to be caused by mutations in the myosin 5B gene (MYO5B). Several mutations in the MYO5B gene have recently been identified in patients with low-GGT cholestasis. A multicenter retrospective and prospective study of 32 children with cryptogenic intrahepatic cholestasis were done. In these individuals, clinical, biochemical, histological, and therapeutic data were evaluated. DNA was taken from peripheral blood, and all patients were investigated using whole-exome sequencing followed by Sanger sequencing.
About 6 of the 32 individuals had MYO5B gene mutations. The median age of illness start for these six 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 hypoechoic stools. In addition, two individuals had intestinal involvement. Transaminases and conjugated bilirubin levels were considerably high, serum bile acids were elevated, and GGT remained normal. Anti-Myo5B immunostaining revealed coarse granules inside the cytoplasm of hepatocytes, but the bile salt export pump was typically expressed at the canalicular membrane in two patients’ liver biopsies. About 6 homozygous or compound heterozygous variations in the MYO5B gene were discovered, three of which had never been documented. Except for one missense variant detected in the isoleucine-glutamine calmodulin-binding motif, all nucleotide changes were found in the myosin motor domain. Researchers found MYO5B causal mutations in 18.7% of individuals with intrahepatic cholestasis, supporting a function for the MYO5B gene in low-GGT cholestasis.