Parental origin of the supernumerary chromosome in trisomy 18 (original) (raw)
Related papers
Non-disjunction of chromosome 18
Human Molecular Genetics, 1998
We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors. The latter finding is unique among human autosomal trisomies, where maternal MI (trisomies 15, 16, 21, 22) or MII (trisomy 18) errors dominate. Of the nine paternally derived cases five were of MII origin but none arose from MI errors. There was some evidence for elevated maternal age in cases with maternal meiotic origin for liveborn infants. Maternal and paternal ages were elevated in cases with paternal meiotic origin. This is in contrast to results from a similar study of non-disjunction of trisomy 21 where paternal but not maternal age was elevated. We find clear evidence for reduced recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms that determine non-disjunction of human chromosomes, consistent with the diversity of findings for other trisomies.
American Journal of Medical Genetics Part A, 2007
Small supernumerary marker chromosomes (sSMC) have been described from all human chromosomes with different sizes and shapes. However, it is difficult to know the clinical manifestations associated with them, because such knowledge depends on the size, presence of euchromatic material, degree of mosaicism and/or uniparental disomy (UPD). Pure trisomy of the whole arm of chromosome 18 (18p), has been described in only a few cases and the general consensus is that there is a mild phenotypic effect. Here we report on a newborn male presenting with an atrial septal defect and a club foot. The high resolution G-band karyotype (550–850 bands) and the molecular cytogenetic techniques revealed in all cells the presence of an sSMC, which was a complex derivative from the short arm of a chromosome 18 (18p) and a centromere of a chromosome 13/21. His healthy mother had the same sSMC in all analyzed cells. With the present case, we support the previous suggestion that this unusual chromosome trisomy 18p has little clinical repercussions. © 2007 Wiley-Liss, Inc.
Isochromosome 18p Results from Maternal Meiosis II Nondisjunction
European Journal of Human Genetics, 1996
Microsatellite analysis with 13 microsatellites spread over 18p was performed to determine the origin of the marker chromosome in 9 patients with addition al metacentric marker chromosomes. Phenotypes and banding patterns sug gested that the markers were isochromosomes 18p. Maternal origin was deter mined in all 8 cases where both parents were available for study. Six cases showed 3 alleles (one paternal, one maternal each in single and double dose) of informative markers located close to the telomere while markers close to the centromere on 18p were reduced to homozygosity (one paternal allele in single dosage and one maternal allele presumably in triple dosage). A similar result was obtained in the patient with no parents available for examination. The other 2 patients were uninformative for maternal hetero-versus homozygosi ty, but at some loci the maternal band was clearly stronger than the paternal one whereas the opposite was never observed. Trisomy 18 differs from triso my 21, XXX and XXY of maternal origin through a preponderance of meiosis II versus meiosis I nondisjunction. Thus, the results of our study and the advanced mean maternal age at delivery of patients with additional i(18p) indicate that in most if not all cases the marker chromosome originates from maternal meiosis II nondisjunction immediately followed by isochromosome formation in one of the 2 maternal chromosomes 18. Possible explanations of these results include a maternally imprinted gene on 18q with a lethal effect if the paternal homologue is lost and a mechanism through which nondisjunc tion in some cases could be connected with isochromosome formation. Key Words Tetrasomy 18p Isochromosome 18p Fluorescence in situ hybridization Chromosome aberration, origin of Meiotic nondisjunction are instances of familial isochromosomes of short arms of acrocentrics containing only heterochromatic material. Supernumerary isodicentric chromosomes containing euchromatic material from the long arm were reported for 14(q 11 and ql2), 15(ql2/13), 21(qll) and 22(qll) [1], KARGER
Origin of the extra chromosome in trisomy 16
Clinical Genetics, 2008
Chromosome analysis was carried out on 22 spontaneous abortuses with trisomy 16 and their parents by means of sequential Q- and C-banding techniques. In seven cases, the extra chromosome No. 16 originated from a non-disjunctional error in the first meiotic division in the mother, and in two cases from an error in the first meiotic division in the father. In two cases, non-disjunction had occurred during the second meiotic division (one in the mother and one in the father). It seems that trisomy 16, although independent of maternal age, most frequently results from a first meiotic non-disjunction in the mother.
A patient with mosaic partial trisomy 18 resulting from dicentric chromosome breakage
American Journal of Medical Genetics Part A, 2005
We present a patient with minor dysmorphic features and a mosaic karyotype with two different abnormal cell lines, both involving abnormalities of chromosome 18. Twenty percent of cells studied (4/20) had 46 chromosomes with a large derivative pseudoisodicentric chromosome 18. This chromosome was deleted for 18pter and duplicated for part of proximal 18p (18p11.2 based on fluorescence in situ hybridization (FISH) studies and all of 18q. The two copies of portions of chromosome 18 were fused in an inverted fashion (duplicated for 18qter->18p11.3). The smaller der(18) was present in 80% of cells studied (16/20) and had a normal q-arm, while the p-arm was missing the subtelomere region but had duplication of a part of 18p. FISH studies showed that the larger derivative 18 contained the 18q subtelomere at each end, but the 18p subtelomere was absent, consistent with fusion of two regions within 18p resulting in deletion of the subtelomeric regions. The smaller der(18) was also missing the 18p subtelomere (with normal 18q as expected). Further testing with BAC clones mapping within 18p11.2 showed that these sequences were duplicated and inverted in both of the der(18)s. These findings lead us to hypothesize that the smaller der(18) was derived from the larger, dicentric 18 following anaphase bridge formation, with breakage distal to the duplicated segment. © 2005 Wiley-Liss, Inc.
Acta Medica Nagasakiensia, 1991
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.
European Journal of Human Genetics, 2011
In this study, we report a familial inversion of chromosome 18, inv(18)(p11.31q21.33), in both members of a consanguineous couple. Their first child had inherited one balanced pericentric inversion along with a recombinant chromosome 18 resulting in dup(18q)/del(18p), and had mild dysmorphic features in the absence of mental and developmental retardation. The second child had received two recombinant chromosomes 18, from the mother a derivative chromosome 18 with dup(18p)/del(18q) and from the father a derivative chromosome 18 with dup(18q)/del(18p). The aberration was prenatally detected; however, as the two opposite aneuploidies were thought to compensate each other, the family decided to carry on with the pregnancy, knowing that uniparental disomy for the segments outside the inversion could have an adverse influence on the development of the child. Uniparental disomy was confirmed by SNP arrays. The child, who has been followed up until the age of 20 months, is healthy and normal. It seems to be the first reported case with two opposite recombinant chromosomes that compensate each other and lead to segmental uniparental disomy for two segments on the chromosome, one maternal and the other paternal.