Molecular analysis of a complex chromosomal rearrangement and a review of familial cases.
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 telomere-specific 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 break-points 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 offspring 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.
Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Maryland.
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Batista
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Pai
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Stetten
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D002869:Chromosome Aberrations / Q000235:genetics*; D002871:Chromosome Banding; D025063:Chromosome Disorders; D002882:Chromosomes, Human, Pair 13; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D008540:Meiosis; D009035:Mothers; D010375:Pedigree; D016615:Telomere / Q000235:genetics; D014178:Translocation, Genetic; D014314:Trisomy