Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18

We report the results of detailed clinical and molecular-cytogenetic studie s in seven patients with ring chromosome 18. Classical cytogenetics and flu orescence in situ hybridization (FISH) analysis with the chromosome 18 pain ting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)( p11.2)147,XX,dup(18) (p11.2),+ r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup (1 8)(p11.32),+r(18) cases. FISH analysis was performed for precise characteri zation of the chromosome 18 breakpoints using chromosome 18-specific short- arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-P CR YAC probes. The breakpoints were assessed with an average resolution of similar to2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions rang ing from 18q21.2 to 18q22.3 (similar to 35 and 9 Mb, respectively) were fou nd, whereas only in four cases could the loss of 18p material be demonstrat ed. In two cases the dup(18) chromosomes were identified as inv dup(18)(qte r --> p11.32::q21.3 --> qter) and inv dup(18)(qter --> p11.32::p11.32 --> p 11.1: :q21.3 --> qter)pat, with no evidence of an 18p deletion. A novel int er-intrachromatid effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18 p-syndromes are compared and correlated with the analyzed genotypes, It has been observed that a short neck with absence of cardiac anomalies may be r elated to the deletion of the 18p material from the r(18) chromosome. (C) 2 001 Wiley-Liss, Inc.