THE SAME MOLECULAR MECHANISM AT THE MATERNAL MEIOSIS-I PRODUCES MONOCENTRIC AND DICENTRIC 8P DUPLICATIONS

We studied 16 cases of 8p duplications, with a karyotype 46,XX or XY,d up(8p), associated with mental retardation, facial dysmorphisms, and b rain defects. We demonstrate that these 8p rearrangements can be eithe r dicentric (6 cases) with the second centromere at the tip of the sho rt arm or monocentric (10 cases). The distal 8p23 region, from D8S349 to the telomere, including the defensin 1 locus, is deleted in all the cases. The region spanning from D8S252 to D8S265, at the proximal 8p2 3 region, is present in single copy, and the remaining part of the abn ormal 8 short arm is duplicated in the dicentric cases and partially d uplicated in the monocentric ones. The distal edge of the duplication always spans up to D8S552 (8p23.1), while its proximal edge includes t he centromere in the dicentric cases and varies from case to case in t he monocentric ones. The analysis of DNA polymorphisms indicates that the rearrangement is consistently of maternal origin. In the deleted r egion, only paternal alleles were present in the patient. In the dupli cated region, besides one paternal allele, some loci showed two differ ent maternal alleles, while others, which were duplicated by FISH anal ysis, showed only one maternal allele. We hypothesize that, at materna l meiosis I, there was abnormal pairing of chromosomes 8 followed by a nomalous crossover at the regions delimited by D8S552 and D8S35 and by D8S252 and D8S349, which presumably contain inverted repeated sequenc es. The resulting dicentric chromosome, 8qter-8p23.1(D8S552)::8p23.1-( D8S35)-8qter, due to the presence of two centromeres, breaks at anapha se I, generating an inverted duplicated 8p, dicentric if the breakage occurs at the centromere or monocentric if it occurs between centromer es.