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Online mutation report
A second heterozygous MDR3 nonsense mutation associated with intrahepatic cholestasis of pregnancy
  1. C Gendrot1,
  2. Y Bacq2,
  3. M-C Brechot3,
  4. J Lansac4,
  5. C Andres1
  1. 1Laboratory of Biochemistry-Molecular Biology and INSERM U316, Hôpital Bretonneau, 37044 Tours Cedex, France
  2. 2Department of Hepatogastroenterology, Hôpital Trousseau, 37044 Tours Cedex, France
  3. 3Laboratory of Biochemistry, Hôpital Trousseau, 37044 Tours Cedex, France
  4. 4Department of Gynaecology and Obstetrics, Clinique du Beffroi, 37044 Tours Cedex, France
  1. Correspondence to:
 Dr C Gendrot, Laboratory of Biochemistry-Molecular Biology and INSERM U316, Hôpital Bretonneau, 37044 Tours Cedex, France;
 gendrot{at}med.univ-tours.fr

https://doi.org/10.1136/jmg.40.3.e32

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    Intrahepatic cholestasis of pregnancy (ICP, 147480) is a liver disorder unique to pregnancy, which usually manifests during late pregnancy and disappears spontaneously after delivery. Maternal symptoms are characterised by generalised pruritus with or without jaundice. The main biological features are increased serum alanine transaminase (ALT) activities and serum bile acid concentrations.1–3 Serum gamma-glutamyl transpeptidase (GGT) activity remains within normal limits or is increased.4,5 The occurrence of ICP carries a risk for the baby because of premature spontaneous delivery or sudden fetal death and pruritus may cause considerable discomfort for the mother.1–3,6 Cholestasis frequently recurs in subsequent pregnancies and rarely during administration of oral contraceptives.5 The cause of ICP is unknown. However, clinical and epidemiological studies suggest mainly hormonal and genetic factors.1–3,7 Genetic factors have been suggested by the existence of familial cases and by the high incidence of ICP in some ethnic groups, such as the Araucanos Indians of Chile.8 The multidrug resistance 3 (MDR3, ABCB4, 171060) gene, localised on 7q21.1, was first reported to be involved in ICP by de Vree et al.9 In a large consanguineous family, subjects affected by a subtype of progressive familial intrahepatic cholestasis called PFIC3 were homozygous for a nonsense mutation in exon 23 (R957X) and women affected by ICP were heterozygous; in another family, the same authors reported a homozygous deletion of exon 6 (426-432del) in a PFIC3 patient with consanguineous, healthy parents.9 A mutation in exon 14 of MDR3 (1744delT) was identified in another large pedigree in which all PFIC patients were homozygous for the mutation and women with ICP were heterozygous.10,11 Dixon et al12 investigated eight women affected by ICP with increased serum GGT activity and no familial history of PFIC. …

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