A bstract Alagille syndrome (AGS) or arteriohepatic dysplasia is a rare but well-defined clinical entity that is usually inherited as an autosomal dominant trait. A lim ited number of patients carry a deletion in chromosome 20p, with 20p 11.23-pi 2.2 as the area of minimal overlap. Recently, a family has been identified in which a balanced translocation with a breakpoint in 20p l 2 co-segregates with the AGS phenotype. Here, we report a three-genera tion family with AGS and in which the affected members have a normal karyotype. Linkage analysis was perfozTned with markers from the 20p candidate region. A lod score of Z=2.96 was obtained with D20S27 at no recombina tion. Combining D20S27 and D20S61 to a single highly informative locus resulted in a maximum lod score of Z -+ 3.56 at 0=0.0. Haplotype analysis positioned AGS between D20S59 and D20S65, markers that define an in terval of about 40 cM. Allelic loss was not observed for the tested markers and no abnormalities in the PAX1 can didate 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.

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2Department of Pediatrics, Groot Ziekengasthuis, 's Hertogenbosch, The Netherlands A family is described with three male sibs suffering from congenital adrenal hypoplasia (CAH). In the two surviving brothers the disease is clinically further characterized by a Duchenne type muscular dystrophy, growth failure and severe mental retardation. Laboratory investigations revealed deficient activities of gonadotrophin and glycerol kinase. The clinical, biochemical and genetic findings in this exceptional family are reported and discussed.