25 - A Rare Case of Russell-Silver and 1p36 Deletion Syndromes

Abstract

receptor gene family, which have been implicated in the etiology of autism and susceptibility to alcohol dependence, and may in tern play a role in the family’s problems with drugs and alcohol. The maternal great grandmother (I.1) did not have the duplications of 16q observed on array in the other family members. However, she was found to have a 461 kb loss on 16q21. This appears to be the same region which separates two of the duplicated regions observed in other family members. FISH analysis has determined the chromosome 16 duplicated regions have been inserted into the short arm of chromosome 4. Further molecular characterization of the duplication, deletions, and insertion are needed for a better understanding of the genomic architecture and mechanism of this complex rearrangement of chromosome 16. The complex rearrangement and copy number aberrations observed in the majority of this family appear to have begun as a unique deletion on chromosome 4p and a unique deletion of chromosome 16q21 in generation I as revealed by microarray analysis. Since at least two of her children received the insertion duplication, she most likely has a balanced version of the insertion. The complex duplication is speculated to have emerged by either nonhomologous end joining recombination (NHEJ) such as in a chromothripsis type event or non-allelic homologous recombination (NAHR) due to microhomology. NAHR mediated by regions of sequence homology at the breakpoints of the 4p deletion and the proximal and distal breakpoints of chromosome 16 segments might best explain the insertion of the 16 into chromosome 4. Further molecular characterization of the breakpoints involved will help elucidate the mechanism which produced this complex aberration.