CYTOLOGICALLY BALANCED T(2,20) IN A 2-GENERATION FAMILY WITH ALAGILLE-SYNDROME - CYTOGENETIC AND MOLECULAR STUDIES

Alagille syndrome is a clinically defined, dominantly inherited disord er affecting the liver, heart, face, eye, and vertebrae. Alagille synd rome has previously been localized to the short arm of chromosome 20, on the basis of reports of a small number of patients with chromosomal deletions of 20p. We undertook a cytogenetic study of patients with A lagille syndrome and identified a family in which a cytologically bala nced translocation between chromosomes 2 and 20, 46,XX/XY,t(2;20)(q21. 3;p12), is segregating concordantly with the disease. The breakpoint o n chromosome 20p in this t(2;20) is consistent with the shortest regio n of overlap demonstrated in the reported deletion patients. This is t he first report of a translocation associated with 20p and Alagille sy ndrome, and this rearrangement confirms the location of the Alagille d isease gene at 20p12. We have established a somatic cell hybrid from a lymphoblastoid cell line from one of the affected individuals that co ntains the derivative chromosome 20 (20qter-->p12::2q21.3-->qter) but not the derivative chromosome 2, the normal chromosome 2, or the norma l chromosome 20. Southern blot and PCR analysis of probes and sequence s from 20p have been studied to define the location of the translocati on breakpoint. Our results show that the breakpoint lies distal to D20 S61 and D20S56 within band 20p12.