Frequency of trisomy 15 and loss of the Y chromosome in adult leukemia.

In the interpretation of the varied and complex cytogenetic counts obtained in analysis of bone marrow (BM) samples for leukemia, loss or gain of certain chromosomes may or may not be significant for prognosis. Loss of the Y chromosome in elderly males is a benign finding. Trisomy 15 is rare and may represent another age-related abnormality, particularly in males, together with -Y. We reviewed 3,242 routine referrals sent to our laboratory for BM cytogenetics, over a period of 34 months. We detected 5 cases with uncomplicated trisomy 15, 3 in males and 2 in females. Three of these patients had the diagnosis of myelodysplastic syndrome (MDS). All 3 males showed a -Y cell line, although the 2 females did not have an X chromosome loss. All 5 patients were alive and well at times varying from 12 months to 4 years post-diagnosis. In the further analysis of our referral cohort, there were 62 males with loss of the Y chromosome as the sole abnormality, and of these 47 (76%), were referred with myeloid disease. The frequency of trisomy 15 in our laboratory was 1/475 referrals, but 1/292 in successful cultures from new patients. This is the first report providing frequency data for trisomy 15. Further data with longer term follow-up is required to establish the significance of trisomy 15 in elderly leukemic patients.     

Frequency of abnormal karyotypes in relation to the ascertainment method in females referred for suspected sex chromosome abnormality

Cytogenetic investigation was carried out on 231 female patients referred for suspected sex chromosome abnormality. Cases were classified into five groups according to reason for referral and chromosome abnormality frequency was estimated. The overall frequency of abnormal karyotypes was 38.5%. The rate of positive identification of chromosome abnormality ranges from 0 in patients with secondary amenorrhoea to 80% in those with Turner phenotype. Our data demonstrate that the indications for referral of female patients with suspected sex chromosome abnormality are not only primary amenorrhoea alone or short stature and primary amenorrhoea without Turner stigmata, but also short stature of unknown etiology without any additional anomaly during childhood.     

A case of trisomy of chromosome 15

We describe a case of trisomy of chromosome 15 in an infant who presented at birth with numerous abnormalities. As far as we are aware this chromosomal abnormality has not been described before. On the basis of this one case there appear to be no features which are specific to this chromosomal abnormality.     

Molecular studies of translocations and trisomy involving chromosome 13

Twenty-four cases of trisomy 13 and one case with disomy 13, but a de novo dic(13,13) (p12p12) chromosome, were examined with molecular markers to determine the origin of the extra (or rearranged) chromosome. Twenty-one of 23 informative patients were consistent with a maternal origin of the extra chromosome. Lack of a third allele at any locus in both paternal origin cases indicate a somatic duplication of the paternal chromosome occurred. Five cases had translocation trisomy: one de novo rob(13q14q), one paternally derived rob(13q14q), two de novo t(13q13q), and one mosaic de novo t(13q13q)/r(13). The patient with a paternal rob(13q14q) had a maternal meiotic origin of the trisomy; thus, the paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13q14q) carrier and most trisomies are maternal in origin, this result should not be surprising; however, it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. Lack of a third allele at any locus in one of the three t(13q13q) cases indicates that it was most likely an isochromosome of postmeiotic origin, whereas the other two cases showed evidence of recombination. One balanced (nontrisomic) case with a nonmosaic 45,−13,−13,t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologues, as has been found for all balanced homologous Robertsonian translocations so far investigated. Thus, it is also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. Despite a maternal origin of the trisomy, we cannot therefore infer anything about the parental origin of the chromosomes 13 and 14 involved in the translocation in the de novo t(13q14q) case nor for the two t(13;13) chromosomes showing a meiotic origin of the trisomy. © 1996 Wiley-Liss, Inc.     

Trisomy 18qter and trisomy mapping of chromosome 18

Four cases of partial trisomy 18q are reported and compared to observations from the literature. The phenotype of 18qter trisomy is described and compared to full trisomy 18.     

女性年龄对卵母细胞纺锤体和染色体构型的影响

目的探讨女性年龄对卵母细胞纺锤体和染色体构型的影响。方法取试管婴儿术后卵龄1天的未受精卵母细胞,采用免疫细胞化学和激光共聚焦术检测卵母细胞纺锤体和染色体构型。结果25~29岁女性卵母细胞Ⅰ级纺锤体和染色体比率分别为33%和31%,显著高于30~34岁(P<0.05)和35~40岁女性(P<0.01);而25~29岁女性卵母细胞的Ⅲ级纺锤体和染色体率均为54%,明显低于30~34岁(P<0.01)和35~40岁女性(P<0.05)。结论卵母细胞纺锤体和染色体构型异常率与女性年龄存在明显的相关性。     

Origin of the extra chromosome in trisomy 16

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.     

Partial trisomy of the long arm of chromosome 7

A baby with partial trisomy 7, 46, XY,t (5;7) (q35;q31) resulting from a familial translocation (5q+,7q-) is reported. The clinical abnormalities of this case closely resemble those of previously reported cases of partial trisomy 7. It is suggested that partial trisomy 7 may represent a clinical entity.     

Patterns of meiotic recombination on the long arm of human chromosome 21

In this study we quantify the features of meiotic recombination on the long arm of human chromosome 21. We constructed a 67. 3-centimorgan (cM) high-resolution, comprehensive, and accurate genetic linkage map of chromosome 21q using 187 highly polymorphic markers covering almost the entire long arm; 46 loci, consisting of mutually recombining marker sets, were ordered with greater than 1000:1 odds and with average interlocus distance of 1.46 cM. These markers were used to accurately identify all exchanges in 186 female and 160 male meioses and to show (1) significant excess of recombination in female versus male meioses, (2) an overall decline in female:male recombination between the centromere and the telomere, (3) greater positive chiasma interference in male than in female meioses, and (4) lack of correlation between exchange frequency and parental age. By comparing the genetic map with the 21q sequence map, we show a general trend of increasing male, but near-constant female, recombination versus physical distance across 21q, explaining the gender-specific recombination effect. The recombination rate varies considerably between genders across 21q but is the greatest (eightfold) in the pericentromeric region, with a rate of approximately 250 kb/cM in females and approximately 2125 kb/cM in males. We used information on the locations of all exchanges to construct an empirical map function that confirms the statistical findings of positive interference. These analyses reveal that occurrence of recombination on 21q is not only gender-specific but also region-specific and that recombination suppression at the centromere is not universal. We also find evidence that male exchange location is highly correlated with gene density.     

Parental origin of the supernumerary chromosome in trisomy 18

Ya-gang X, Robinson WP, Spiegel R, Binkert F, Ruefenacht U, Schinzel AA. Parental origin of the supernumerary chromosome in trisomy 18. Clin Genet 1993: 44: 57–61. Munksgaard, 1993
The parental origin of an extra chromosome in Edwards syndrome has been investigated in 23 families by the combination of the VNTR probe pERT25, two microsatellite polymorphisms for D18S34 and D18S40, and several two-allele polymorphisms. Of the 23 cases, 22 were informative, with 17 (77%) being maternal and 5 (23%) paternal in origin. These results support the previous investigations, suggesting that trisomy 18 is predominantly of maternal origin, although a higher rate of paternally derived cases was observed than previously reported. A significant increase in maternal age was found to be associated with meiotic nondisjunction. Parental age was increased in both the maternally and paternally derived cases, but the size of the latter class was small and did not reach statistical significance.     

Enzyme thermosensitivity of leukocytes with trisomy for chromosome 21

The thermosensitivity of glucose-6-phosphate dehydrogenase and myeloperoxidase was studied in lysates of leukocytes from patients with Down's syndrome. A statistically significant increase in temperature sensitivity of these two enzymes was discovered in leukocytes trisomic for chromosome 21 compared with the control. The differences observed may be based on an increased frequency of mutation injuries in the aberrant cells and also of abnormal post-translation modification of the protein molecules.Academic Group of Corresponding Member of the Academy of Medical Sciences of the USSR Professor E. F. Davidenkova, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Laboratory of Human Cytogenetics, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 1, pp. 41–44, January, 1979.     

Co-occurrence of chromosome 22q11.2 microdeletion and trisomy 21 mosaicism

This report describes a patient who had some phenotypic features of Down syndrome (DS) as well as severe conotruncal cardiac anomalies, including pulmonary atresia with ventricular septal defect (tetralogy of Fallot with pulmonary atresia), confluent pulmonary arteries, a large left-sided ductus arteriosus, left aortic arch, aberrant right subclavian artery, and secundum atrial septal defect. Cytogenetic and fluorescence in situ hybridization (FISH) analysis was carried out on peripheral blood lymphocytes and skin fibroblasts using probes specific for the chromosomal loci 21q22.13 to 21q22.2 and locus 22q11.2. This revealed 47,XX+21/46,XX mosaicism at a rate of 15:85 and the micro-deletion 22q11.2 (del22q11.2). Some patients'congenital cardiac anomalies are atypical for the type of mosaicism or aneuploidy. The case suggests that association of del22q11.2 should be considered in patients with chromosomal mosaicism or aneuploidy who also have particular conotruncal cardiac defects.     

低剂量电离辐射引起小鼠胚胎上皮细胞中染色体不分离的研究

目的探讨低剂量电离辐射与细胞减数分裂染色体不分离的关系。方法7~8w ICR雌性小鼠经PMGS和hCG促排卵后分别给予不同剂量(<1.5Gy)及相同剂量不同次数的Cs137γ-射线照射后使其与同龄未受照射雄鼠交配,17~19d后取胎鼠的上皮组织进行细胞培养,制备染色体标本并观察、计数。结果母鼠经电离辐射后,子代体细胞中染色体非整倍体率和超二倍体率明显增高,且呈现剂量-相应和次数-相应。结论低剂量电离辐射是引起卵细胞染色体不分离的重要环境因子。     

Pure partial trisomy for long arm of chromosome 9.

A case of a 4-year-old boy with trisomy of the long arm of chromosome 9 is described (46,XY, der (9), t (9;9) (q32;q12)). The trisomy is probably the result of a translocation of the long arm of the chromosome from one homologue to the other in a parental gonad. The clinical features of the child which include severe developmental retardation, bird-like facies, tapered fingers, and flexion contractures of the legs are similar to those of the few cases described of trisomy of the whole chromosome.     

Human fetal ovarian culture permits meiotic progression and chromosome pairing process

BACKGROUND: The female meiotic process seems to be crucial for aneuploidy in humans. The first stages of mammalian female meiosis take place during the fetal period. Therefore, only little is known about female meiosis. The goal of this study was to develop a culture technique that permits human oocytes to progress through meiotic prophase, to provide a system to study human female meiosis. METHOD: Fetal ovaries from four cases were cultured up to 35 days in alpha-minimal essential medium, 2% human serum albumin, 5 microg/ml insulin, 5 microg/ml transferrin, 5 ng/ml selenium and 100 IU/ml penicillin-100 microg/ml streptomycin. RESULTS AND CONCLUSIONS: Although ovarian response to culture conditions varied, human oocytes survived in vitro up to 5 weeks. In three cases, we observed significant variation in stages of meiosis among the cultures. The homologous chromosome pairing process was studied for the first time in cultured oocytes, and the results suggested that the pairing process was completed following the same features described previously for euploid oocytes, as followed by the chromosome-13 pairing process and synaptonemal complex formation. Although a higher proportion of degenerated oocytes were observed as culture time increased, we also observed oogonial entrance to meiotic prophase.     

Mitotic and meiotic instability of a telomere association involving the Y chromosome

Constitutional telomere associations and jumping translocations (JTs) are rare events and usually occur post-zygotically. We report a telomere association involving the Y chromosome which "jumped" during meiosis. A 21-year-old woman was referred for amniocentesis due to non-immune hydrops seen in a previous pregnancy. Cytogenetic analysis of the amniocytes showed a 45,X,tas(Y;15)[4]/45,X[16] karyotype with the long arm of the Y chromosome attached to the end of the short arm of chromosome 15. Parental chromosome analyzes revealed a tas(Y;19)[63]/45,X[7] karyotype in the father with Yq attached to the end of the short arm of chromosome 19. A phenotypically normal male was born and blood chromosome analysis confirmed a 45,X,tas(Y;15)[39]/45,X[10]/46,XY[1] karyotype. Two other male children have 46,XY karyotypes, which further demonstrates the instability of the tas(Y;19) in meiosis. Fluorescence in situ hybridization (FISH) analysis with probes for theY-centromere, the Yqh region, the shared Xq/Yq telomere and SRY showed hybridization on the tas(Y;19) and tas(Y;15). A chromosome 19p specific subtelomeric probe showed hybridization to the tas(Y;19) in the father. In addition, a probe for the simple telomeric sequences TTAGGG showed positive hybridization to the junction of the associations. The presence of TTAGGG telomere repeats and unique telomere sequences indicate that the Y;15 and Y;19 associations occur with no detectable loss of any sequences. The interstitial telomere sequences at the junction of the telomere association may explain the mitotic and meiotic instability of the association.     

Directly inherited partial trisomy of chromosome 6p identified in a father and daughter by chromosome microdissection

Cytogenetic analysis of a 4 year old girl with developmental delay and dysmorphic features showed extra chromosomal material of unknown origin on 20p (46,XX,add(20)(p13)). Familial chromosome studies showed direct inheritance of add(20)(p13) from the father, who had a similar, albeit milder, phenotype. Fibroblast chromosome studies of the father showed no karyotype mosaicism. The additional material could not be identified on the basis of the G banding pattern owing to its small size and ambiguous banding pattern. Chromosome microdissection of the unknown material was performed, the DNA was amplified and labelled using degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) and reverse painted to the proband's cells to show the karyotype 46,XX,der(20)t(6;20) (p23;p13), conferring partial trisomy 6p and presumed partial monosomy for 20p. Chromosome microdissection has made possible the first reported case of directly inherited partial trisomy 6p.