A missense mutation in FIC1 is associated with greenland familial cholestasis.

[benign recurrent intrahepatic cholestasis]

Greenland familial cholestasis is a severe form of intrahepatic cholestasis described among indigenous Inuit families in Greenland . Patients present with jaundice , pruritus , bleeding episodes , and steatorrhea , and die in childhood due to end-stage liver disease . We investigated the possibility that Greenland familial cholestasis is caused by a mutation in FIC 1 , the gene defective in patients with progressive familial intrahepatic cholestasis type 1 and many cases of benign recurrent intrahepatic cholestasis . Using single -strand conformation polymorphism analysis and sequencing of the FIC 1 exons , a missense mutation , 1660 G-->A (D 554 N ), was detected and was shown to segregate with the disease in Inuit patients from Greenland and Canada . Examination of liver specimens from 3 Inuit patients homozygous for this mutation revealed bland canalicular cholestasis and , on transmission electron microscopy , coarsely granular Byler bile , as previously described in patients with progressive familial intrahepatic cholestasis type 1 . These data establish Greenland familial cholestasis as a form of progressive familial intrahepatic cholestasis type 1 and further underscore the importance of unimpeded FIC 1 activity for normal bile formation .

Diseases
Validation

Diseases presenting "intrahepatic cholestasis" symptom

benign recurrent intrahepatic cholestasis

zellweger syndrome

This symptom has already been validated