Molecular characterization of the marker chromosome associated with cat eye syndrome.

Cat eye syndrome (CES) is associated with a supernumerary bisatellited marker chromosome which is derived from duplicated regions of 22pter-22q11.2. In this study we have used dosage and RFLP analyses on 10 CES patients with marker chromosomes, by using probes to five loci mapped to 22q11.2. The sequences recognized by the probes D22S9, D22S43, and D22S57 are in four copies in all patients, but the sequences at the more distal loci, D22S36 and D22S75, are duplicated only in some individuals. D22S36 is present in three copies in some individuals, and D22S75 is present in two copies in the majority of cases. Only three individuals have a duplication of the most distal locus examined (D22S75), and these individuals have the largest marker chromosomes identified in this study. From the dosage analysis it was found that the marker chromosomes are variable in size and can be asymmetric in nature. There is no obvious correlation between the severity of the phenotype and the size of the duplication. The distal boundary of the CES critical region (D22S36) is proximal to that of DiGeorge syndrome, a contiguous-gene-deletion syndrome of 22q11.2.