MECHANISMS OF SMALL RING FORMATION SUGGESTED BY THE MOLECULAR CHARACTERIZATION OF 2 SMALL ACCESSORY RING CHROMOSOMES DERIVED FROM CHROMOSOME-4

Molecular cloning of a microdissected small accessary ring chromosome 4 from a moderately retarded and dysmorphic patient has been performed to identify the origin of the ring chromosome. FISH was performed wit h cosmids identified with the cloned, microdissected products and with other markers from chromosome 4. The present study clearly demonstrat es that the small ring in this patient originates from three discontin uous regions of chromosome 4: 4p13 or 14, the centromere, and 4q31. It is suggested that the origin of the ring chromosome is a ring involvi ng the entire chromosome 4, which has then been involved in breakage a nd fusion events, as a consequence of DNA replication generating inter locked rings. A second severely retarded and dysmorphic patient also h ad a small accessary ring derived from chromosome 4. FISH studies of t his ring are consistent with an origin from a contiguous region includ ing the centromere to band 4q12. It is apparent that there are at leas t two mechanisms for the formation of small ring chromosomes. This add s a further complication in any attempt to ascertain common phenotypes between patients known to have morphologically similar markers derive d from the same chromosome.