title: Progressive familial intrahepatic cholestasis (PFIC): evidence for genetic heterogeneity by exclusion of linkage to chromosome 18q21-q22.
abstract: Progressive familial intrahepatic cholestasis (PFIC) is the second most common form of familial intrahepatic cholestasis. The genes for PFIC and for a milder form of the disease, benign recurrent intrahepatic cholestasis (BRIC), were recently mapped to a 19-cM region on chromosome 18q21-q22. The results suggest that PFIC and BRIC are allelic diseases. We have studied 11 Swedish patients from eight families with clinical and biochemical features consistent with PFIC. The families were genotyped for markers D18S69, D18S64, D18S55 and D18S68, spanning the PFIC candidate region. Unexpectedly, the segregation of haplotypes excluded the entire region in three families, and no indications for shared haplotypes were found in the patients of the six remaining families. A four-point linkage analysis of all families excluded linkage from D18S69 to D18S55 (Zmax < -5). Thus, our data strongly suggest the presence of a second, yet unknown, locus for PFIC. The results indicate that great care should be taken when using 18q markers for prenatal diagnosis and genetic counseling for the disease.
authors.affiliation: Department of Clinical Genetics, Uppsala University Children's Hospital, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Arnell
authors.forename: A
authors.initials: A
authors.lastname: Nemeth
authors.forename: G
authors.initials: G
authors.lastname: Annerén
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D002780:Cholestasis, Intrahepatic / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18; D018450:Disease Progression; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D008297:Male
chemical_list: D005819:Genetic Markers