SEARCH FOR 22Q11 DELETION AND LINKAGE STU DIES IN FAMILIAL CASES OF NON-SYNDROMAL FAMILIAL CONOTRUNCAL MALFORMATIONS

Conotruncal malformations are one of the major criteria of the Di Geor ge syndrome. Nearly 90 % of subjets with this syndrome have been shown to have a 22q11 deletion of a part of the long arm of chromosome 22. The authors set out to determine the role of the 22q11 region in the g enesis of non-syndromic familial conotruncal malformations. The famili es were selected on the following criteria: at least 2 members affecte d; the members had to have a ''conotruncal malformation'' (truncus art eriosus, tetralogy of Fallot, interruption of the aortic arch, ...). T yping with a microsatellite (x) marker localised in the region usually deleted, deletion was searched for in affected and non-affected membe rs. A study of the transmission of the alleles from generation to gene ration was made with x and three other microsatellite markers (w, y, z ) which cover the pericentromeric region of 22q. Six families fulfilli ng the inclusion criteria were presented. Of the 11 affected members, 9 had no deletion in the region where the microsatellite x is localise d. In 2 cases it was not possible to arrive at a formal conclusion at this stage of the study. All individuals of the 6 recruited families w ere typed with the 4 microsatellites. Computer analysis (Linkage progr am) of the results obtained showed that the markers w and x were very close to each other (a recombination rate between these two markers TH ETA = 0.001). Linkage analysis seems to infirm the 22q11 region in the genesis of conotruncal malformations (total lodscore - 2.74 for x, fo r THETA = 0), at least in the 6 families studied to date. A greater nu mber of families needs to be studied to improve our understanding of t he transmission of these non-syndromic familial conotruncal malformati ons.