Non-disjunction of chromosome 21, alphoid DNA variation, and sociogenetic features of Down syndrome.
Vorsanova S G,Iourov I Y,Beresheva A K,Demidova I A,Monakhov V V,Kravets V S,Bartseva O B,Goyko E A,Soloviev I V,Yurov Y B
TSitologiia i genetika
The analysis of non-disjunction of chromosome 21 and alphoid DNA variation by using cytogenetic and molecular cytogenetic techniques (quantitative fluorescence in situ hybridization) in 74 nuclear families was performed. The establishment of possible correlation between alphoid DNA variation, parental age, environmental effects, and non-disjunction of chromosome 21 was made. The efficiency of techniques applied was found to be 92% (68 from 74 cases). Maternal non-disjunction wasfound in 58 cases (86%) and paternal non-disjunction - in 7 cases (10%). Post-zygotic mitotic non-disjunction was determined in 2 cases (3%) and one case was associated with Robertsonian translocation 46,XX,der(21;21)(q10;q10), +21. Maternal meiosis I errors were found in 43 cases (64%) and maternal meiosis II errors--in 15 cases (22%). Paternal meiosis I errors occurred in 2 cases (3%) and paternal meiosis I errors--in 5 cases (7%). The lack of the correlation between alphoid DNA variation and non-disjunction of chromosome 21 was established. Sociogenetic analysis revealed the association of intensive drug therapy of infectious diseases during the periconceptual period and maternal meiotic non-disjunction of chromosome 21. The correlation between non-disjunction of chromosome 21 and increased parental age as well as exposure to irradiation, alcohol, tobacco, mutagenic substances was not found. The possible relevance of data obtained to the subsequent studies of chromosome 21 non-disjunction is discussed.
Molecular analysis of mosaicism for two different de novo acrocentric rearrangements demonstrates diversity in Robertsonian translocation formation.
Berend S A,Canún S,McCaskill C,Page S L,Shaffer L G
American journal of medical genetics
Robertsonian translocations (ROBs) involving chromosome 21 occur in about 5% of individuals with Down syndrome. ROBs are the most common chromosomal rearrangements in humans and are formed through whole arm exchanges of any two acrocentric chromosomes. The de novo formation of ROBs occurs at exceptionally high rates. The present case concerns a child with mosaic Down syndrome who has two cell lines that contain two different de novo ROBs: 45,XX,rob(14;21)(q10;q10) and 46,XX,rea(21;21)(q10;q10),+21. To elucidate the mechanisms by which the rearrangements formed, somatic cell hybrids were constructed to allow the parental origins of the chromosomes involved in the ROBs to be distinguished. The analysis of the hybrids showed that the rob(14q21q) must have formed postzygotically because it contained a maternal chromosome 14 and a paternal chromosome 21. Furthermore, hybrid analysis of the rea(21q21q) demonstrated two copies of the same chromosome from the mother and thus, by definition, was an isochromosome [i(21q)]. All free-lying chromosomes 21 isolated in hybrids were of maternal origin. These chromosomes may have originated from either of the patient's cell lines. We present four hypotheses for the formation of the two cell lines of this child. This case is part of an ongoing project to determine the mechanism(s) of de novo ROB formation and the results differ from the other de novo rob(14q21q) studied in our laboratory (n = 7) in that all previously studied translocations were maternally derived, leading to the conclusion that most de novo rob(14q21q) occur in oogenesis. The current case illustrates that other mechanisms may contribute to ROB formation.
Cytogenetic and epidemiological findings in Down syndrome: England and Wales 1989-2009.
Morris Joan K,Alberman Eva,Mutton David,Jacobs Patricia
American journal of medical genetics. Part A
This study describes the characteristics of karyotypes leading to phenotypic Down syndrome (trisomy 21) in 29,256 cases diagnosed between 1989 and 2009 in England and Wales included in the National Down Syndrome Cytogenetic Register (NDSCR). The frequency of occurrence of the different karyotypes, proportions diagnosed prenatally, sex ratios, mean maternal age, and proportions of mothers with recurrences were analyzed. Nearly 97% of all cases were free trisomy 21; 2.9% contributory trisomy 21, 0.3% double or triple aneuploidies; 1% of all were mosaics. Mean maternal age of free trisomy 21 cases was 35 years, 54% were male, and 1% of mothers had recurrences. Free trisomy 21 mosaics had a lower mean maternal age (33 years), a lower proportion of males (39.5%), and 2.5% of mothers had recurrences. The majority of contributory translocations were Robertsonian or rea (21;21). Their mothers were younger, particularly those of Robertsonian translocations (28 years). Of the Robertsonian der (14;21) translocations of known parental origin, 54% were de novo, 41% maternal and 5% paternal and 15.8% of mothers of those of maternal origin had recurrences. Multiple aneuploidies have the highest proportion of males (67%), highest proportion of mosaics (40%), a mean maternal age of 37 years, and no mothers had a recurrence. The size of this national register allowed the frequency of occurrence of the rarer karyotypes of Down syndrome to be estimated and their epidemiology described.
10.1002/ajmg.a.35248
Pure duplication 21q21.2-->qter due to a rea(21) in a Down syndrome girl. Remarks on nomenclature.
Dominguez M G,Arteaga-Alcaraz G,Rivera H
Genetic counseling (Geneva, Switzerland)
We report on an 8-year-old girl with a typical Down syndrome phenotype and a 46,XX,rea(21)(qter-->p12::q21.2-->qter).ish rea(21)(qter-->pl2::q21.2-->qter)(LSI 21++,AML1++) karyotype; the mother had normal chromosomes but the father was unavailable. The great resemblance of the patient's rearranged chromosome to the rec(21)dup(q) from a parental pericentric inversion suggests that it would be better depicted as a recombinant-like chromosome. Altogether, 13 recombinant-like chromosomes of de novo or unknown (parents not karyotyped) origin have been described. Although these rearranged chromosomes should formally be described as derivatives because no parental inversion is identified, we underlie that the unofficial term recombinant-like would be more appropriate because no "multiple aberrations within a single chromosome" (as required by the ISCN) have been proved, not to mention that the term derivative usually designates abnormal chromosomes resulting from a translocation between non homologous chromosomes. Accordingly, we prefer to identify such rearrangements of a single chromosome precisely with the more neutral and sanctioned term rea (expanding its use to designate a rearranged chromosome) coupled with the lengthy description of the abnormal chromosome. We assume that the rea(21) chromosomes result from illegitimate recombination between non allelic homologous LCRs located in both the short and long arms.
Mirror-symmetric duplicated chromosome 21q with minor proximal deletion, and with neocentromere in a child without the classical Down syndrome phenotype.
Barbi G,Kennerknecht I,Wöhr G,Avramopoulos D,Karadima G,Petersen M B
American journal of medical genetics
We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21. This der(21) chromosome has a deletion of 21p and of proximal 21q, whereas the main portion of 21q is duplicated leading to a mirror-symmetric appearance with the mirror axis at the breakpoint. The centromere is only characterized by a secondary constriction (with a centromeric index of a G chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specific or with all human centromeres alpha satellite DNA shows no cross hybridization. Thus, the marker chromosome represents a further example of an "analphoid marker with neocentromere." Molecular analysis using polymorphic markers on chromosome 21 verified a very small monosomic segment of the proximal long arm of chromosome 21, and additionally trisomy of the remaining distal segment. Although trisomic for almost the entire 21q arm, our patient shows no classical Down syndrome phenotype, but only a few minor anomalies found in trisomy 21 and in monosomy of proximal 21q, respectively.
Discordant direct and culture results following chorionic villus sampling and the diagnosis of a third cell line in the fetus.
Phillips O P,Velagaleti G V,Tharapel A T,Shulman L P
Prenatal diagnosis
We report a case of discordant non-mosaic karyotypes following chorionic villus sampling (CVS). A 45,XX,der(21;21)(q10;q10) karyotype was found on direct preparation of cytotrophoblasts and 46,XX was found on long-term culture of mesenchymal core cells. Analysis of amniotic fluid cells and fetal tissue revealed a third karyotype: 46,XX,+21,der(21;21)(q10;q10). Had only culture analysis been performed, follow-up studies might not have been undertaken. This case demonstrates the importance of direct CVS preparation in helping to identify fetal abnormalities, and the need for follow-up of discordant CVS results.
Recurrent abortions and down syndrome resulting from Robertsonian translocation 21q; 21q.
Kolgeci Selim,Azemi Mehmedali,Ahmeti Hasan,Dervishi Zeqir,Sopjani Mentor,Kolgeci Jehona
Medical archives (Sarajevo, Bosnia and Herzegovina)
AIM:The purpose of the present research was a presentation of case report of Robertsonian translocation composed of homologous chromosomes 21q;21q and reproductive risk found in the family affected by this type oftranslocation. METHODS:Cytogenetic diagnosis has been done on chromosome preparations of lymphocytes cultured from peripheral blood by Moorhead method. RESULTS:Analyses of cytogenetic diagnosis was performed on the couple who has been through 10 spontaneous miscarriages and two additional births with Down syndrome. The woman had Robertsonian translocation between homologous chromosomes 21: 45XX,der(21;21)(q10;q10), and there was no change in her phenotype, whereas her husband had a normal phenotype and karyotype: 46, XY. Their first child with Down syndrome symptoms did not undergo the cytogenetic analysis. By cytogenetic analysis it was discovered that their second child has Trisomy 21 with Robertsonian translocations between homologous chromosomes 21: 46,XY,+21,der(21;21) (q10;q10)mat, and that he inherited it from his mother. CONCLUSION:Chromosomal aberration that our patient suffered from and that is presented in this paper has caused spontaneous miscarriages and birth of children with Down syndrome. Based on cytogenetic analysis in prenatal diagnosis and genetic consultation of affected family with Robertsonian translocation 21q;21q, it is unlikely to select healthy offspring by a parent with that aberration.
10.5455/medarh.2012.66.350-352
Evidence for nonhomologous meiotic coorientation in man.
Journal of human genetics
Nonhomologous meiotic co-orientation (NMC) was postulated for humans a half of century ago to explain the association between the presence of a rearranged chromosome(s) and the occurrence of aneuploidy for an unrelated chromosome ("interchromosomal effect", ICE). However subsequent studies did not support meiotic nature of ICE phenomenon. At the same time, NMC model can be fruitful for solving a number of problems regarding the etiology of human aneuploidy. Published and own data on the offspring of 322 parental carrier of chromosomal abnormality were analyzed according to the carrier's gender. In families with transmission of der(21;21), among patients with maternally derived trisomy 21 (T21), there is a typical male-biased sex ratio (SR), with 33 males/28 females. Among patients with paternally derived T21, five-fold male prevalence is observed (16 males/3 females), p = 0.0373. In families with maternal balanced non-contributing rearrangement (Rea), SR was male-biased among T21 patients, both those inherited (42 males/30 females) and not inherited the Rea (17 males/11 females). However, in families with paternal balanced Rea, there is an impressive difference between T21 offspring with transmitted paternal Rea and those not inherited paternal Rea, 49 males/21 females vs 4 males/15 females, p = 0.0003. A female predominance is also observed among non-trisomic offspring of paternal carriers of gonadal mosaicism for T21 (2 males/12 females), but not in non-trisomic offspring of maternal carriers (19 males/16 females), p = 0.0253. Unusual sex ratios in offspring of male carriers are considered as the result of NMC of a chromosome abnormality with the X chromosome operating in spermatogenesis.
10.1038/s10038-023-01123-7
Low-level mosaic trisomy 21 due to mosaic unbalanced Robertsonian translocation of 46,XX,+21,der(21;21) (q10;q10)/46,XX at amniocentesis in a pregnancy associated with a favorable fetal outcome, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, cytogenetic discrepancy among various tissues and perinatal progressive decrease of the trisomy 21 cell line.
Taiwanese journal of obstetrics & gynecology
OBJECTIVE:We present prenatal diagnosis of mosaic trisomy 21 at amniocentesis associated with unbalanced Robertsonian translocation in the fetus and a favorable fetal outcome. CASE REPORT:A 41-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Her husband was 41 years old. Amniocentesis revealed a karyotype of 46,XX,+21,der(21;21) (q10;q10)[8]/46,XX[18], consistent with 30.8% (8/26 colonies) mosaicism for trisomy 21. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22,X) × 2 with no genomic imbalance. Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XX,+21,der(21;21) (q10;q10)[2]/46,XX[25], consistent with 7.4% (2/27 colonies) mosaicism for trisomy 21. Cord blood sampling revealed the result of 46,XX and rsa X(P095) × 2, 13,18,21(P095) × 2. Prenatal ultrasound findings were normal. At 23 weeks of gestation, she underwent cord blood sampling which revealed a karyotype of 46,XX. At 26 weeks of gestation, she was referred for genetic counseling. No repeat amniocentesis and continuing the pregnancy were advised. The mother had a karyotype of 46,XX, and the father had a karyotype of 46,XY. At 38 weeks of gestation, a 3476-g, phenotypically normal baby was delivered. The cord blood had a karyotype of 46,XX,+21,der(21;21) (q10;q10)[1]/46,XX[39] (2.5% mosaicism). The placenta had a karyotype of 46,XX,+21,der(21;21) (q10;q10) (40/40 cells). When follow-up at age two months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XX (40/40 cells), and aCGH analysis on buccal mucosal cells resulted no genomic imbalance. CONCLUSION:Low-level mosaic trisomy 21 at amniocentesis due to mosaic unbalanced Robertsonian translocation with a normal cell line can be associated with a favorable fetal outcome, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, cytogenetic discrepancy among various tissues and perinatal progressive decrease of the trisomy 21 cell line.
10.1016/j.tjog.2024.09.014
Monozygotic twins discordant for homologous Robertsonian translocation trisomy 21 of 46, XX, + 21, der (21;21) (q10; q10) in a twin-to-twin transfusion syndrome, case report.
Cao Dingya,Sun Jimei,Li Nan,Li Zhihua,Liu Weiqiang,Chen Min
BMC pregnancy and childbirth
BACKGROUND:Monozygotic twins are nearly identical in genotype and phenotype because monozygotic twins arise from one fertilized oocyte. In all cases of discordant karyotype in monozygotic twins, trisomy 21 accounts for about one in 385,000. Monozygotic twins discordant for Robertsonian translocation trisomy 21 of the der (21;21)(q10;q10), in which the additional chromosome originates from the father is rare. CASE PRESENTATION:A 28-year-old parous woman, G3P1A0, came to our institution for a dating scan at 8 weeks of gestation. The transvaginal ultrasound examination demonstrated a monochorionic diamniotic pregnancy. She and her husband were healthy, with no family history of trisomy 21 or other congenital diseases. The ultrasound examination of nuchal translucency thickness was discordant in twins at 13 weeks (twin A, NT 1.4 mm with CRL being 65 mm; twin B, NT 7.8 mm with CRL being 69 mm). At 17 weeks, twin A was normal, but ventricular septal defect and the hypoplastic left heart was detected in twin B. The deepest vertical pocket was 18 mm in twin A (oligohydramnios) and 102 mm in Twin B (polyhydramnios). The bladder in twin A was absent. Ultrasound findings indicated TTTS Stage II. Amniocentesis was performed for the two fetuses. The karyotyping results revealed 46, XX in twin A but 46,XX,+ 21,der (21;21)(q10;q10) in twin B. For twin B, the parents opted for selective fetal termination by radiofrequency ablation. The procedure was uneventful. At 40 weeks, twin A was born with a birth weight of 4120 g by vaginal delivery. CONCLUSIONS:The early detection of discordant karyotype and twin-to-twin transfusion syndrome is beneficial to the early intervention. In monozygotic twins with a discordant anomaly, the discordant karyotype should be considered.
10.1186/s12884-021-03587-x