Molecular analysis of a complex chromosomal rearrangement and a review of familial cases

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Abstract
A complex chromosome rearrangement (CCR) involving chromosomes 7, 8, and 13 was detected in a phenotypically normal woman ascertained through her mentally retarded son with abnormal phenotype. He had a karyotype with 47 chromosomes including an extra der(13). In initial banding studies the CCR in the mother was interpreted as a three‐way translocation. Fluorescence in situ hybridization with whole chromosome libraries and a telomerespecific probe was used to better characterize the rearrangement. Combined data allowed us to reinterpret the CCR as a translocation 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 than do de novo CCRs; 2) familial transmission is mainly observed through female carriers although the origin of de novo cases is paternal; 3) an apparent excess of balanced female carriers among the off‐spring of index carriers was noted; and 4) meiotic segregation resulting in malformed liveborn infants is most frequently due to adjacent‐1 segregation, followed by 4:2 segregation; no adjacent‐2 segregation was observed.