50 PROBANDS WITH EXTRA STRUCTURALLY ABNORMAL CHROMOSOMES CHARACTERIZED BY FLUORESCENCE IN-SITU HYBRIDIZATION

Extra structurally abnormal chromosomes (ESACs) are small supernumerar y chromosomes often associated with developmental abnormalities and ma lformations, We present 50 probands with ESACs characterized by fluore scence in situ hybridization using centromere-specific probes and chro mosome-specific libraries, ESAC-specific libraries were constructed by flow sorting and subsequent amplification by DOP-PCR, Using such ESAC -specific libraries we were able to outline the chromosome regions inv olved, Twenty-three of the 50 ESACs were inverted duplications of chro mosome 15 [inv dup(15)], including patients with normal phenotypes and others with similar clinical symptoms. These 2 groups differed in siz e and shape of the inv dup(15), Patients with a large inv dup(15), whi ch included the Prader-Willi region, had a high risk of abnormality, w hereas patients with a small inv dup(15), not including the Prader-Wil li region, were normal, ESACs derived from chromosomes 13 or 21 appear ed to have a low risk of abnormality, while one out of 3 patients with an ESAC derived from chromosome 14 had discrete symptoms, One out of 3 patients with an ESAC derived from chromosome 22 had severe anomalie s, corresponding to some of the manifestations of the cat eye syndrome , Small extra ring chromosomes of autosomal origin and ESACs identifie d as i(12p) or i(18p) were all associated with a high risk of abnormal ity. (C) 1995 Wiley-Liss, Inc.