Parental Origin and Mechanism of Formation of de novo Chromosome Abnormalities : 25 Cases of Numerical and Structural Abnormalities Determined by Restriction Fragment Length Polymorphisms
Parental origin and mechanism of formation of de novo numerical and structural chromosome abnormalities were studied in 25 cases using RFLPs as genetic markers. In 8 of the 10 (5 autosomal and 5 X-chromosomal) numerical abnormalities studied, the origin and the mechanism of formation were ascertained. Of five 21-trisomics, two resulted from a maternal second meiotic nondisjunction, one (a 46/47,+21 mosaic) from mitotic nondisjunction of a paternally-derived chromosome 21, and the remaining two were uninformative. The origin and the mechanism of formation of the additional X chromosomes in the five patients with poly-X chromosomes (a case of XXXXX and four of XXXXY) studied were identical. They all arose through three nondisjunctions at maternal meiosis: once at the first meiosis and simultaneously twice at the second meiosis. These observations indicate that the parental origin of numerical abnormalities is not different between autosomes and X chromosome, the maternal origin being predominant. Of the 15 structural abnormalities studied, the origin was ascertained in 11. An interstitial deletion of chromosome 15 [del(15)(q11.1q12)] in 2 of 5 cases arose at paternal meiosis. A 15q15q translocation in one of 2 cases resulted from centric misdivision of a maternal chromosome 15 followed by duplication of its long-arm, and thus the translocated chromosome is in the condition of maternal uniparental disomy. A case of partial monosomy 21 (monosomy for 21pter-q21.3) resulted from a translocation between paternal chromosomes 2 and 21. The origin of X-chromosomal structural abnormalities in 3 cases were paternal and that in the other 4 cases maternal. Partial X-chromosome duplication [dup(Xp)] in one patient arose through an unequal sister chromatid exchange in the paternal X chromosome, partial deletion [del(Xp)] in one arose at the paternal meiosis, isochromosome X [i(Xq)] in three resulted from centric fission followed by duplication of Xq in a maternal X chromosome, isodicentric chromosome X [inv dup(Xq)] in one arose through an unequal exchange between sister chromatids in a maternal. X chromosome, and ring chromosome X [r(X)] in the other case arose at maternal meiosis. These results on the structural abnormalities suggest that the de novo abnormalities due to events involving centromere disruption arise predominantly during oogenesis, while those due to simple breakage-reunion events occur preferentially during spermatogenesis
