CHARACTERIZATION OF FAMILIAL PARTIAL 10P TRISOMY BY CHROMOSOMAL MICRODISSECTION, FISH, AND MICROSATELLITE DOSAGE ANALYSIS

Unbalanced translocations are a frequent cause of multiple congenital anomalies in children. Translocations as small as 2-5 Mb of DNA are de tectable by G-banding under optimal conditions. Some of these small tr anslocations are visible but cannot be characterized cytogenetically d ue to the lack of characteristic banding on Giemsa preparations. We ha ve combined chromosomal microdissection and fluorescence in situ hybri dization (FISH) to identify the origin of a small translocated segment in three members of a family with a derivative chromosome 9 and multi ple anomalies, including several ophthalmologic anomalies. We microdis sected the abnormal region of the derivative 9 chromosome and used thi s DNA to generate a FISH probe. This probe hybridized to distal 10p on the metaphase spread of the proband, indicating the origin of the tra nslocated segment. A whole 10p FISH probe confirmed the origin by hybr idizing to the translocated segment of the derivative chromosome. FISH was then performed with a whole chromosome 9 painting probe and exclu ded the presence of a reciprocal, balancing translocation. We then stu died the chromosome 10 partial duplication with microsatellite markers to better characterize the chromosomal segment that caused these phen otypic features, By examining the involved areas with distal 10p and 9 p microsatellite markers, we were able to demonstrate a minimum of 9 M b of trisomic 10p DNA with a chromosomal breakpoint between 10p14-10p1 5. We then compared this family's clinical findings to those of indivi duals with partial 10p trisomy who had been reported in the literature . The clinical phenotypes seen in this family are similar to, but mild er than, the phenotypes of persons with the larger partial trisomies o f 10p that were diagnosable by cytogenetic analysis alone, This study shows that microdissection and DNA markers can be used to precisely de fine small translocations that are difficult to identify by convention al G-banded chromosome analysis.