Localization of Alagille syndrome to 20p11.2-p12 by linkage analysis of a three-generation family

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 id...

Full description

Saved in:
Bibliographic Details
Published in:Human genetics 1995-06, Vol.95 (6), p.687-690
Main Authors: HOL, F. A, HAMEL, B. C. J, GEURDS, M. P. A, HANSMANN, I, NABBEN, F. A. E, DANIËLS, O, MARIMAN, E. C. M
Format: Article
Language:English
Subjects:
Alagille Syndrome - epidemiology
Alagille Syndrome - genetics
Alagille's syndrome
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
chromosome 20
Chromosome Mapping
Chromosomes, Human, Pair 20 - genetics
deletion mutant
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Female
haplotypes
Humans
Indonesia - ethnology
linkage analysis
Lod Score
Male
man
Medical sciences
Netherlands - epidemiology
Pedigree
Sequence Deletion
Translocation, Genetic
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0340-6717
1432-1203
DOI:10.1007/BF00209488