MOLECULAR ANALYSIS OF A COMPLEX CHROMOSOMAL REARRANGEMENT AND A REVIEW OF FAMILIAL CASES

A complex chromosome rearrangement (CCR) involving chromosomes 7, 8, a nd 13 was detected in a phenotypically normal woman ascertained throug h her mentally retarded son with abnormal phenotype. He had a karyotyp e with 47 chromosomes including an extra der(13). In initial banding s tudies the CCR in the mother was interpreted as a three-way translocat ion, Fluorescence in situ hybridization with whole chromosome librarie s and a telomere-specific probe was used to better characterize the re arrangement. Combined data allowed us to reinterpret the CCR as a tran slocation and an insertion. A review of 35 familial CCRs involving at least three chromosomes led to the following observations: 1) familial CCRs tend to have fewer chromosomes involved and fewer breakpoints th an do de novo CCRs; 2) familial transmission is mainly observed throug h female carriers although the origin of de novo cases is paternal; 3) an apparent excess of balanced female carriers among the offspring of index carriers was noted; and 4) meiotic segregation resulting in mal formed liveborn infants is most frequently due to adjacent-1 segregati on, followed by 4:2 segregation; no adjacent-2 segregation was observe d. (C) 1994 Wiley-Liss, Inc.