Fa. Hol et al., LOCALIZATION OF ALAGILLE SYNDROME TO 20P11.2-P12 BY LINKAGE ANALYSIS OF A 3-GENERATION FAMILY, Human genetics, 95(6), 1995, pp. 687-690
Alagille syndrome (AGS) or arteriohepatic dysplasia is a rare but well
-defined clinical entity that is usually inherited as an autosomal dom
inant trait. A limited number of patients carry a deletion in chromoso
me 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 rep
ort a three-generation family with AGS and in which the affected membe
rs have a normal karyotype, Linkage analysis was performed with marker
s from the 20p candidate region. A lod score of Z=2.96 was obtained wi
th D20S27 at no recombination, Combining D20S27 and D20S61 to a single
highly informative locus resulted in a maximum lod score of Z=+3.56 a
t Theta=0.0. Haplotype analysis positioned AGS between D20S59 and D20S
65, markers that define an interval of about 40 cM. Allelic loss was n
ot observed for the tested markers and no abnormalities in the PAX1 ca
ndidate gene were detected. These findings demonstrate that the locus
on chromosome 20p could be responsible for AGS in cytogenetically norm
al patients and argues for a general role of this locus in the aetiolo
gy of AGS.