Progressive familial intrahepatic cholestasis with high γ-glutamyltranspeptidase levels in Taiwanese infants: Role of MDR3 gene defect?
Journal
Pediatric Research
Journal Volume
50
Journal Issue
1 I
Pages
50-55
Date Issued
2001
Author(s)
Chang P.-S.
Hsu H.-C.
Abstract
MDR3 P-glycoprotein mediates canalicular phospholipid transport in hepatocytes. Defects in the MDR3 gene have been found to cause a subtype of progressive familial intrahepatic cholestasis (PFIC) with high γ-glutamyltranspeptidase (GGT) levels. Affected children develop proliferation of biliary epithelium, portal inflammation, and biliary cirrhosis. The frequency of MDR3 mutations in patients with high GGT-PFIC is unclear. There have been no Asian patients reported to carry MDR3 mutations. To determine the role of MDR3 defects in chronic cholestatic patients, we studied six Taiwanese children from five families who presented high GGT-PFIC among 47 patients with infantile onset chronic intrahepatic cholestasis. Sequence analysis of MDR3 cDNA from liver tissues was performed. Only one patient had mutation in the MDR3 gene. This patient had a homozygous 719-bp deletion (nucleotide 287 to 1005) of liver cDNA encompassing exon 5 to 9 and leading to protein truncation. The onset age was 1 y in contrast with the other five patients who presented neonatal cholestasis. Four patients without mutation, including one sibling pair, exhibited histologic features of prominent portal fibrosis leading to advanced biliary cirrhosis that were indistinguishable from the case of MDR3 mutation. We concluded that mutations in MDR3 accounted for approximately 2% (1/47) of infantile onset chronic cholestasis in Taiwan. Those patients presenting high GGT-PFIC with early onset cholestasis but without MDR3 mutation probably had inheritable disorders remaining to be clarified.
SDGs
Other Subjects
complementary DNA; gamma glutamyltransferase; gene product; glycoprotein P; multidrug resistance protein; multidrug resistance protein 3; unclassified drug; article; biliary cirrhosis; clinical article; DNA sequence; familial disease; female; gamma glutamyl transferase blood level; gene deletion; gene mutation; genetic disorder; human; human cell; infant; intrahepatic cholestasis; liver fibrosis; male; mdr3 gene; newborn; onset age; priority journal; progressive familial intrahepatic cholestasis; Taiwan
Publisher
Lippincott Williams and Wilkins
Type
journal article