A second heterozygous MDR3 nonsense mutation associated with intrahepatic cholestasis of pregnancy

摘要: Intrahepatic cholestasis of pregnancy (ICP, 147480) is a liver disorder unique to pregnancy, which usually manifests during late and disappears spontaneously after delivery. Maternal symptoms are characterised by generalised pruritus with or without jaundice. The main biological features increased serum alanine transaminase (ALT) activities bile acid concentrations.1–3 Serum gamma-glutamyl transpeptidase (GGT) activity remains within normal limits increased.4,5 occurrence ICP carries risk for the baby because premature spontaneous delivery sudden fetal death may cause considerable discomfort mother.1–3,6 Cholestasis frequently recurs in subsequent pregnancies rarely administration oral contraceptives.5 unknown. However, clinical epidemiological studies suggest mainly hormonal genetic factors.1–3,7 Genetic factors have been suggested existence familial cases high incidence some ethnic groups, such as Araucanos Indians Chile.8 multidrug resistance 3 ( MDR3 , ABCB4 171060) gene, localised on 7q21.1, was first reported be involved de Vree et al .9 In large consanguineous family, subjects affected subtype progressive intrahepatic called PFIC3 were homozygous nonsense mutation exon 23 (R957X) women heterozygous; another same authors deletion 6 (426-432del) patient consanguineous, healthy parents.9 A 14 (1744delT) identified pedigree all PFIC patients heterozygous.10,11 Dixon 12 investigated eight GGT no history PFIC. …