title: Localization of Alagille syndrome to 20p11.2-p12 by linkage analysis of a three-generation family.
abstract: Alagille syndrome (AGS) or arteriohepatic dysplasia is a rare but well-defined clinical entity that is usually inherited as an autosomal dominant trait. A limited number of patients carry a deletion in chromosome 20p, with 20p11.23-p12.2 as the area of minimal overlap. Recently, a family has been identified in which a balanced translocation with a breakpoint in 20p12 co-segregates with the AGS phenotype. Here, we report a three-generation family with AGS and in which the affected members have a normal karyotype. Linkage analysis was performed with markers from the 20p candidate region. A lod score of Z = 2.96 was obtained with D20S27 at no recombination. Combining D20S27 and D20S61 to a single highly informative locus resulted in a maximum lod score of Z = +3.56 at theta = 0.0. Haplotype analysis positioned AGS between D20S59 and D20S65, markers that define an interval of about 40 cM. Allelic loss was not observed for the tested markers and no abnormalities in the PAX1 candidate gene were detected. These findings demonstrate that the locus on chromosome 20p could be responsible for AGS in cytogenetically normal patients and argues for a general role of this locus in the aetiology of AGS.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: Hol
authors.forename: B C
authors.initials: BC
authors.lastname: Hamel
authors.forename: M P
authors.initials: MP
authors.lastname: Geurds
authors.forename: I
authors.initials: I
authors.lastname: Hansmann
authors.forename: F A
authors.initials: FA
authors.lastname: Nabben
authors.forename: O
authors.initials: O
authors.lastname: Daniëls
authors.forename: E C
authors.initials: EC
authors.lastname: Mariman
mesh_terms: D016738:Alagille Syndrome / Q000453:epidemiology / Q000235:genetics*; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005260:Female; D006801:Humans; D007214:Indonesia / Q000208:ethnology; D008126:Lod Score; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D010375:Pedigree; D017384:Sequence Deletion; D014178:Translocation, Genetic