DELETIONS OF 20P12 IN ALAGILLE-SYNDROME - FREQUENCY AND MOLECULAR CHARACTERIZATION

Alagille syndrome is an autosomal dominant disorder comprising cholest asis (associated with intrahepatic bile duct paucity), characteristic facial appearance, and cardiac, ocular and skeletal defects, Multiple patients have been reported with deletions or translocation involving 20p11.23-p12, providing evidence for the localization of the disease g ene to this region. Fifty-six Alagille syndrome patients have been stu died by cytogenetic and/or molecular analysis to determine the frequen cy of detectable abnormalities of 20p12. Two of fifty-six patients stu died by cytogenetic analysis had abnormalities: an interstitial deleti on in one patient and a translocation in another. Of forty-five patien ts studied by molecular analysis, three were found to have deletions o f 20p, including the two patients identified with cytogenetic abnormal ities. Molecular and molecular cytogenetic (FISH) analysis of the tran slocation (46,XX,t(2;20)(q21.3p12)) demonstrated a deletion at the tra nslocation breakpoint, The deletions identified in the three patients are overlapping, contributing to the delineation of an Alagille syndro me critical region within 20p12. This region lies between markers D20S 41 and D20S162. The frequency of detectable cytogenetic abnormalities of 20p12 in this group of Alagille patients is 2/56 (3.6%), and the fr equency of molecular deletions is 3/45 (6.7%). This is considerably lo wer than the frequency of deletions observed in contiguous gene deleti on syndromes suggesting that Alagille syndrome may be caused by the al teration of a single gene. (C) 1997 Wiley-Liss, Inc.