CLINICAL AND MOLECULAR CHARACTERIZATION OF PATIENTS WITH DISTAL 11Q DELETIONS

Jacobsen syndrome is caused by segmental aneusomy for the distal end o f the long arm of chromosome 11, Typical features include mild to mode rate psychomotor retardation, trigonocephaly, facial dysmorphism, card iac defects, and thrombocytopenia, though none of these features are i nvariably present. To define the critical regions responsible for thes e abnormalities, we studied 17 individuals with de novo terminal delet ions of 11q. The patients were characterized in a loss-of-heterozygosi ty analysis using polymorphic dinucleotide repeats. The breakpoints in the complete two-generation families were localized with an average r esolution of 3.9 cM. Eight patients with the largest deletions extendi ng from 11q23.3 to 11qter have breakpoints, between D11S924 and D11S13 41. This cytogenetic region accounts for the majority of 11q(-) patien ts and may be related to the FRA11B fragile site in 11q23.3. One patie nt with a small terminal deletion distal to D11S1351 had facial dysmor phism, cardiac defects, and thrombocytopenia, suggesting that the gene s responsible for these features may lie distal to D11S1351. Twelve of 15 patients with deletion breakpoints as far distal as D11S1345 had t rigonocephaly, while patients with deletions distal to D11S912 did not , suggesting that, if hemizygosity for a single gene is responsible fo r this dysmorphic feature, the gene may lie distal to D11S1345 and pro ximal to D11S912.