1/8. Chromosome duplications and deletions and their mechanisms of origin.Duplications and deletions of the same gene loci or chromosome regions are known to produce different clinical manifestations and are significant factors in human morbidity and mortality. Extensive cytogenetic and molecular cytogenetic studies with cosmid and YAC probes in two patients with unique mosaicism for reciprocal duplication-deletion allowed us to further understand the origin of these abnormalities. The first patient's mosaic karyotype was 46,XX, inv dup(11) (q23q13)/46,XX,del(11)(q13q23). The second patient had a 46,XY,dup(7)(p11.2p13)/46,XY,del(7)(p11.2p13)/46,XY karyotype. fluorescence in situ hybridization studies on the first patient placed the two breakpoints near the folate-sensitive fragile sites FRA11A and FRA11B. The presence of repeated sequences responsible for these fragile sites may have been involved in the patient's duplication-deletion. Our investigation leads us to conclude that, in addition to known mechanisms (such as unequal crossovers between homologs, unequal sister chromatid exchanges, excision of intrachromatid loops, and meiotic recombination within a single chromatid), duplication-deletion can also arise by the formation of an overlying loop followed by an uneven crossover at the level of the dna strand.- - - - - - - - - - ranking = 1keywords = chromatid (Clic here for more details about this article) |
2/8. Inverted duplications are recurrent rearrangements always associated with a distal deletion: description of a new case involving 2q.We studied the case of a subject with an inverted duplication of 40 cM of 2q33-q37 concurrent with a 10 cM deletion of the distal 2q, the latter not being detectable by cytogenetics. Microsatellite analysis demonstrated the absence of maternal alleles in the deleted region and a double dosage for one of the maternal alleles in the duplication region. We hypothesised that this type of rearrangement occurs at meiosis I, while the two homologues are synapsed for most of their length. The presence of inverted duplicons in the same chromosome arm would favour the partial refolding of one homologue into itself so leading to the intrachromatid synapsis and recombination of the inverted repeats. The arising recombinant chromosome is deleted for the region beyond the most distal repeat and with the chromatids joined together at the level of the region located between the two duplicons. At meiosis II, the two linked chromatids can join the opposite poles provided that a breakage between the two centromeres occurs leading to a duplicated/deleted chromosome and a simply deleted chromosome. This model can be extended to all the so-called inverted duplication cases and to part of the terminal deletions. In fact the finding that, in our invdup(2q), the entire 40 cM duplication region involves only one of the two maternal alleles, indeed indicates that the abnormal crossover occurs between sister chromatids. The phenotype associated with our 2q rearrangement led us to narrow the critical region for the Albright-like syndrome to 10 cM in the subterminal 2q region.- - - - - - - - - - ranking = 1.3333333333333keywords = chromatid (Clic here for more details about this article) |
3/8. Inv dup(22), del(22)(q11) and r(22) in the father of a child with digeorge syndrome.We here report a unique inherited case of digeorge syndrome. The asymptomatic father had a mosaic karyotype with a 21q11 deletion in three different cell lines. In two of the cell lines there was an additional supernumerary inv dup(22) or an r(22), respectively. In the third cell line the del(22) was the sole anomaly. FISH analysis showed that both the inv dup(22) and the r(22) included the DGS region. We hypothesize that an inter-chromosomal recombination between inverted repeats, together with a recombination between sister chromatids during meiosis I, gave rise to a deletion of 22q11 as well as an inv dup(22) containing the DGS region. The inv dup(22) was later rearranged into a ring chromosome during mitosis which was subsequently lost during cell division, thereby resulting in three different cell lines. This is the first case reported with an inv dup(22) and a del(22)(q11) in the same cell line. Our findings support a related mechanism in the formation of these two rearrangements mediated by low-copy repeats.- - - - - - - - - - ranking = 0.33333333333333keywords = chromatid (Clic here for more details about this article) |
4/8. Loss of subtelomeric sequence associated with a terminal inversion duplication of the short arm of chromosome 4.We report on a 4(1/2)-year-old girl, who presented with multiple minor anomalies consistent with trisomy for 4p. GTG-banding identified a de novo terminal inversion duplication of distal 4p, dup(4)(p16.3p15.3). fluorescence in situ hybridization (FISH) with a wcp4 probe confirmed the chromosome 4 origin of the additional material. FISH with a 4p subtelomere probe, D4F26, showed no signal on the dup(4) chromosome identifying a deletion of this region. Molecular analysis of 4p STS loci confirmed the subtelomeric deletion and showed loss of the paternal allele in this region. The paternal origin of the deleted region and homozygosity for one of the two paternal alleles within the region of the duplication suggests that a sister chromatid rearrangement on the paternal chromosome 4 was involved in the formation of the dup(4) chromosome. To date, the best characterized mechanisms of formation of chromosome duplications are terminal inversion duplications of 8p, which were shown to be derived from rearrangements at maternal meiosis-I. Our data show that mechanisms other than a maternal meiosis-I rearrangement can lead to the formation of terminal inversion duplications. FISH analysis with the appropriate subtelomeric probes is warranted in terminal inversion duplications to check for associated deletions.- - - - - - - - - - ranking = 0.33333333333333keywords = chromatid (Clic here for more details about this article) |
5/8. Submicroscopic terminal deletion of 1p36.3 and Xp23 hidden in complex chromosome rearrangements: independent mechanism of telomere restitution on the two chromatids.In this study, we report two cases each with a complex chromosome rearrangement concealing a submicroscopic terminal deletion. The first case had a mos 46,XX,der(1)t(1;9)(p36.3;p13). ish der(1)(wcp9 , 1ptel-, 9ptel , pan tel )[88]/46,XX. ish del(1)(1ptel -, 9ptel -, pan tel )[12] karyotype. Scrutiny by FISH using wcp 9, 1ptel, 9ptel, and pan telomeric probes found a subtelomeric 1ptel deletion on the der(1) in the abnormal cell line and on a chromosome 1 in the apparently normal cell line. The telomere (TTAGGG)n, however, was present on the terminal ends of both copies of chromosome 1 in the apparently normal and abnormal cell lines. The second case had a de novo mos 46,X,der(X)t(X;22)(p22.3;q11.2),inv dup(22)(q11.2).ish der(X)(wcpX ,wcp22 ,KAL , STS -,Xptel -,BCR ),inv dup(22)(wcp22 ,TUPLE ,BCR -)[85]/45,X,der(X)t(X;22)(p22.3;q11.2),- 22[15].ish der(X)(wcpX ,wcp22 , KAL ,STS -,Xptel -,BCR ) karyotype. FISH probes identified a terminal Xpter deletion, distal to the KAL gene. The two rearrangements are hypothesized to have been initiated by a terminal deletion. We propose a model for the formation of the rearrangement in Case 1, which invokes independent telomere stabilization of the sister chromatids. A terminal deletion 1pter in meiosis, was followed by acquiring or regenerating a telomere (TTAGGG)n cap on one chromatid and the other chromatid was involved in a translocation with a chromosome 9 chromatid. Following segregation of this chromosome the viable cell line survives to form the mosaic karyotype. Our findings suggest that subtelomeric deletions should be ruled out in cases with complex and simple rearrangements involving the terminal regions.- - - - - - - - - - ranking = 2.6666666666667keywords = chromatid (Clic here for more details about this article) |
6/8. Del(18)(q12.2q21.1) caused by a paternal sister chromatid rearrangement in a developmentally delayed girl.monosomy of 18q12.3 has been reported in only 16 cases, in one as a mosaic with a normal cell line. Abnormal behaviour, developmental delay, normal measurements, and minor facial anomalies including ptosis, bilateral epicanthus, strabismus, short and slightly down-slanting palpebral fissures, and full cheeks are characteristic manifestations. We report on a 26-month-old girl with del(18)(q12.2q21.1) and typical phenotype. Microsatellite mediated haplotype analysis showed approximately 12 Mb deletion and demonstrated that the deletion was most likely formed during paternal meiosis by a rearrangement between the grandpaternal sister chromatids.- - - - - - - - - - ranking = 1.6666666666667keywords = chromatid (Clic here for more details about this article) |
7/8. Dissociation of tdic chromosomes: about a t(15;18)(p11;p11) leading to 18p monosomy.A 10-month-old girl with monosomy due to a de novo 45,XX,-15,-18, tdic(15;18)(p11;p11) karyotype is described. The abnormal chromosome underwent dissociation into two telocentrics in 5/200 (2.5%) metaphases. This and other comparable instances indicate that, in addition to criss-cross separation of the dicentric chromatids, the characteristics of the anomalous reunion also influence the rate of dissociation. Besides, the mean maternal (31.2) and paternal (35.1) ages in this subtype of 18p monosomy are significantly increased.- - - - - - - - - - ranking = 0.33333333333333keywords = chromatid (Clic here for more details about this article) |
8/8. Skewed inactivation of an x chromosome deleted at the dystrophin gene in an asymptomatic mother and her affected daughter.A girl with severe Becker muscular dystrophy and apparently normal chromosomes had a heterozygous deletion for exons 51, 52, and 53 of the dystrophin gene. This deletion was transmitted by her mother, who was unaffected. To differentiate the normal and the deleted X chromosomes, fluorescence in situ hybridization (FISH) was applied to metaphase chromosomes, using probes for both exons 51 and 52, which are only 388 and 113 base pairs long, respectively. FISH signals were observed in one or both chromatids of one chromosome, but never on both chromosomes, suggesting the lack of hybridization on the deleted x chromosome. Using 5-bromodeoxyuridine incorporation to differentiate the late (inactive) and the early replicating (active) X chromosomes, 77% of the signals were observed on the active X chromosomes in the mother. This percentage was only 18% in the daughter, suggesting that skewed inactivation of the X chromosomes was responsible for the phenotypic differences.- - - - - - - - - - ranking = 0.33333333333333keywords = chromatid (Clic here for more details about this article) |