Trisomy 7, trisomy 10, and loss of the Y chromosome in short-term cultures of normal kidney tissue

Numerical chromosome aberrations are common in several types of malignant tumors. Recently, trisomy 7 and loss of the Y chromosome were described in cultures from nonneoplastic tissue, making the significance of these aberrations as cancer-associated changes doubtful. We herein report the mosaic occurrence of trisomy 7 in four consecutive short-term cultures initiated from normal kidney tissue. Smaller clones with trisomy 10 were present in three cases, and the only culture established from a male also showed mosaic loss of the Y chromosome.     

A prenatal counseling conundrum: mosaic trisomy 16. A case study presenting cognitive functioning and adaptive behavior

We report developmental data on a patient prenatally diagnosed with mosaic trisomy 16. At age six years her intellectual functioning, academic achievement, and adaptive behavior are normal. The myriad of findings among cases prenatally diagnosed with mosaic trisomy 16 are discussed. The diagnosis presents a dilemma for genetic counselors and clinicians.     

Parental trisomy 21 mosaicism.

A family with three children with trisomy 21 in which the mother is a phenotypically normal, trisomy 21/normal mosaic was studied. Chromosome 21 fluorescent heteromorphisms were used to document that two of the three number 21's in two of the Down syndrome offspring were of maternal origin. Five cytogenetic surveys in which both parents of a child with trisomy 21 were studied have been reviewed. From these data, it is estimated that 3% of couples producing a child with trisomy 21 can be explained by parental mosaicism. From 17 informative sibships, with one parent mosaic, the segregation ratio was estimated to be 0.43 +/- 0.11.     

Mosaic trisomy 15 and hemihypertrophy.

We report a case of mosaic trisomy 15 with mental retardation, facial dysmorphism, and hemihypertrophy, but no manifestations of Prader-Willi or Angelman syndromes. Mosaic trisomy 15 (11%) was discovered at the amniocentesis. Uniparental disomy for chromosome 15 was excluded by molecular analysis. Post-natal blood karyotype and examination were normal. Mosaic was confirmed on skin fibroblasts, placenta and cord. Evolution was marked by progressive right hemi-hypertrophy, and developmental delay. Our case is the first patient reported with hemihypertrophy associated with mosaic trisomy 15. The relevant literature is reviewed.     

A case with mosaic partial duplication of 1q: prenatal and postmortem clinical and cytogenetic evaluations

Partial trisomy 1q including different segments of the long arm is a rare cytogenetic anomaly. Especially the cases with mosaic proximal tandem duplication of 1q included a longer fragment are very rare. Cases who have partial 1q trisomy showed large phenotypic variation due to the differences in size of the duplicated segments of 1q. The clinical phenotype of most cases is characterized by multiple congenital anomalies especially including central nervous system and developmental delay. We describe a prenatally diagnosed case with mild cerebral ventriculomegaly and karyotype with mosaic pure trisomy of chromosome 1q [(46,XX/46,XX,dup(1)(q21qter)]. Phenotypic postmortem examination showed cranial asymmetry, flat and broad nasal bridge, anteverted nostrils, hypertelorism, retrognathia, abnormal pinnae, hypoplasic thumbs, long fingers and toes, mediodorsal curvature of the 4th and 5th toes and posterior prominence of the heel was observed. Autopsy confirmed the ventriculomegaly. Postmortem chromosome preparation from skin culture, cord blood and intracardiac blood confirmed the mosaic pure trisomy of chromosome 1q.     

Chromosome studies in 500 induced abortions.

A survey of the chromosome constitution in 500 induced abortions (5-12 menstrual weeks) was undertaken over a period of 1 1/2 years. There were 34 cases (6.8%) of gross chromosome anomalies: 2 cases of trisomy A; 5 of trisomy C (including XXX and XXY); 1 of mosaic trisomy C; 4 of trisomy D; 2 of trisomy E; 2 of trisomy G; 1 of double trisomy E and G; 1 of XYY; 4 of monosmy C (including XO); 2 of mosaic monosomy C; 1 of mosaicism of ring D chromosome; 1 of extra small metacentric chromosome; 3 of triploidy (including triploidy with double trisomy C and G); and 5 of tetraploidy and its mosaicism. An increased risk for the occurrence of trisomic anomalies was found with advancing age of the mothers. In contrast, the production of monosomies was not age-related. Trisomies were the most common type of anomalies and were found almost at random, regardless of the characteristics of chromosomes. Neither satellited nor small chromosomes were predominantly involved in the formation of chromosome anomalies.     

Trisomy of chromosome No. 10 in mosaic (author's transl)

A case of trisomy of chromosome No. 10 in mosaic is described in a boy who died at the age of 6 months. The frequency of pathological cells is less than 30% (28% from lymphocytes, 20% from fibroblasts); it is possible, anyway, to rule out the hypothesis of a cellular cloning in vitro, since the trisomy 10 was observed in two different cultures, terminated after 48 and 72 hours. The parents' karyotype was normal, except for a litte number (6%) of cells with trisomy 10 from cultured lymphocytes of the mother. The morphological features of the present case are compared with those of the boy described by Higurashi et al. in 1969 (mosaic of trisomy 10, with a higher frequency of pathological cells).     

Duplication of the short arm of chromosome 9. Analysis of five cases

Summary Five females with duplication of the short arm of one chromosome 9 are reported, one tetrasomic and four trisomic for 9p. The tetrasomy is due to an isochromosome 9p while the trisomies are due in one case to an intrachromosomal duplication present in lymphocytes but not in fibroblasts, two are secondary to translocations with chromosomes 22 and 13 respectively, and one is a mosaic with a cell line with an additional deleted chromosome 9 present in lymphocytes and fibroblasts. This analysis indicates that duplications 9p may result in impairment of ovarian function. The phenotypic differences between trisomy and tetrasomy 9p are discussed.     

A rare case: mosaic trisomy 22.

A 9-year-old female child of healthy parents (mother: 43 years, father: 44 years) was referred to our center because of severe mental retardation. While pedigree analysis was not contributory, two older sibs were normal and healthy. Physical examination revealed facial dysmorphism, microcephaly and hyperflexibility of all joints. Her chromosome constitution showed a mosaic pattern; mos 46,XX[98]/47,XX,+22[2]. So skin biopsy was performed and mosaic trisomy 22 was confirmed with FISH analysis (46,XX[73]/47,XX,+22[27]). Physical features of this case seemed consistent with her mosaic constitution. This report would be a demonstrative example to show the significant contribution of FISH in states of mosaicism.     

Autopsy Report of a 7-Year Old Patient with the Mosaic Trisomy 13

We present here a long survival case of a patient with the mosaic form of trisomy 13 who died of aspiration pneumonia at the age of 7 years and 4 months. The autopsy revealed olfactory aplasia and fenestration of the septum pellucidum, and dilated lateral ventricles and atrophic hippocampus. Furthermore, there were numerous “torpedos” (i.e., swollen fusiform Purkinje cell axons), mostly in the granular layer underneath the Purkinje cell layer, and, occasionally, in the granular layer. Similar neuropathological findings have been reported in elderly cases of essential tremor, Parkinson’s disease, or Alzheimer’s disease. Precise mechanism for this axonal change is still unclear. These pathological changes have never previously been reported in the literature on trisomy 13, and the present patient is one of the oldest autopsied individuals with the mosaic trisomy 13.     

Double autosomal/gonosomal mosaic aneuploidy: study of nondisjunction in two cases with trisomy of chromosome 8

We report cytogenetic and molecular investigations performed in two cases of mosaic trisomy 8 combined with mosaic sex chromosome aneuploidy. In a 35-year-old female, presenting with short stature, gonadal dysgenesis, and a multiple congenital anomalies/mental retardation syndrome typical of trisomy 8, chromosome analysis from peripheral lymphocytes showed the presence of three cell lines, whose karyotypes were 45,X (59.2%), 46,X,+8 (1.2%), and 47,XX,+8 (39.6%), respectively. The same cell lines were found in a skin fibroblast culture, though in different proportions. The second patient, a 9-month-old male with multiple skeletal abnormalities, showed a 47,XY,+8 and a 47,XXY cell line in both peripheral lymphocytes (61.7% and 38.3%, respectively) and skin fibroblasts (92.8% and 7.2%, respectively). To determine the events underlying the origin of these complex karyotypes we performed Southern blot and polymerase chain reaction (PCR) analysis using polymorphic DNA markers from the X chromosome and from chromosome 8. Both supernumerary chromosomes 8, and, in case 2, the two X chromosomes, appeared to be identical, lacking detectable recombination events. We conclude that, in both cases, the most likely mechanism underlying the origin of the mosaic cell lines was formation of a normal zygote, followed by mitotic errors during early divisions.     

Trisomy 16 confined to chorionic villi and unfavourable outcome of pregnancy.

Two cases of trisomy 16 confined to placental tissue associated with an unfavourable outcome of the pregnancy are reported. In the first case, after a diagnosis of an apparent non-mosaic trisomy 16 at chorionic villi sample (CVS), an intrauterine fetal death occurred at the 22nd week. In the second case a mosaic with trisomy 16 was found in chorionic villi and the fetus was still-born at 38 weeks. From a comparison of their cases with those of the literature, the authors conclude that a trisomy 16 confined to placental tissue has a negative effect on fetal growth and pregnancy outcome.     

Molecular studies of chromosomal mosaicism: relative frequency of chromosome gain or loss and possible role of cell selection.

Studies of uniparental disomy and origin of nonmosaic trisomies indicate that both gain and loss of a chromosome can occur after fertilization. It is therefore of interest to determine both the relative frequency with which gain or loss can contribute to chromosomal mosaicism and whether these frequencies are influenced by selective factors. Thirty-two mosaic cases were examined with molecular markers, to try to determine which was the primary and which was the secondary cell line: 16 cases of disomy/trisomy mosaicism (5 trisomy 8, 2 trisomy 13, 1 trisomy 18, 4 trisomy 21, and 4 involving the X chromosome), 14 cases of 45,X/46,XX, and 2 cases of 45,X/47,XXX. Of the 14 cases of mosaic 45,X/46,XX, chromosome loss from a normal disomic fertilization predominated, supporting the hypothesis that 45,X might be compatible with survival only when the 45,X cell line arises relatively late in development. Most cases of disomy/trisomy mosaicism involving chromosomes 13, 18, 21, and X were also frequently associated with somatic loss of one (or more) chromosome, in these cases from a trisomic fertilization. By contrast, four of the five trisomy 8 cases were consistent with a somatic gain of a chromosome 8 during development from a normal zygote. It is possible that survival of trisomy 8 is also much more likely when the aneuploid cell line arises relatively late in development.     

Trisomy 8

Summary Trisomy 8, in mosaic or non-mosaic form is an extremely rare chromosomal condition in man. Liveborn subjects usually present with mental retardation, bone and joint anomalies and a variety of other physical anomalies. The mental retardation associated with the condition is, however, usually moderate compared to that found in other viable human autosomal trisomic conditions. The present report describes a trisomy 8 mosaic male subject with normal IQ and near-normal phenotype, ascertained through infertility. Chromosome studies on peripheral blood lymphocytes reveal a pure trisomy 8 constitution; cultured skin fibroblasts show 46,XY/47,XY+8 mosaicism. At meiosis, the extra No. 8 chromosome is missing from the germ line. The testicular histology indicates a germ cell maturation arrest in many spermatocytes and the patient is severely oligospermic. Biochemical studies to assay levels of glutathione reductase, a red cell enzyme, the gene for which resides in chromosome 8, show increased levels in the trisomy 8 patient compared with controls.     

46,XX,t(15;21)/47,XX,15p-,+21 mosaicism in a child with Down's syndrome

We report here the first case of a mosaic Down's syndrome in which both clones are trisomic for chromosome 21, one of them (90%) by a Robertsonian translocation (15;21) appearing de novo, and the other (10%) by an additional chromosome 21. Three hypotheses can explain the appearance of such a mosaic: that of a chimera formed by the fusion of two trisomy 21 zygotes, one of which had a Robertsonian translocation, the other an additional trisomy 21 zygote; that of a fusion between a chromosome 15 and a chromosome 21 in one of the early segmentation blastomeres of a trisomy 21 zygote; the more probable hypothesis of the occurrence of a fission at the break-attachment point of a Robertsonian translocation (15;21) in one of the cells arising from the early postzygotic divisions of a zygote which was a trisomy 21 by Robertsonian translocation (15;21).     

Transposition of great arteries in an infant born after prenatal diagnosis of trisomy 20 mosaicism

We report a case of prenatally diagnosed mosaic trisomy 20 in cells cultured from amniotic fluid. Trisomy 20 was present in 7 cells (13 percent) in a total of 52 investigated cells. Following the normal findings of an ultrasound scan, the couple decided to continue the pregnancy. A dysmorphic infant was born at the 38 weeks of gestation with generalized dysmorphic features and multiple cardiac anomalies including transposition of great arteries. Chromosome analysis on both cord blood and placenta at birth revealed a normal 46,XX karyotype. This patient is the first case of a liveborn infant with mosaic trisomy 20 cells detected in amniotic fluid culture with transposition of great arteries, atrioventricular concordance and ventricoarterial discordance.     

Uniparental disomy and the phenotype of mosaic trisomy 20: a new case and review of the literature

Mosaic trisomy 20 is one of the most commonly reported chromosome abnormalities detected prenatally, but is rare postnatally. Many studies have hypothesized that uniparental disomy (UPD) may play a role in phenotype variability, but this has not been widely studied. Here we report an additional case of mosaic trisomy 20 with altered pigmentation, in which UPD was not found, and we review the literature.     

Maternal uniparental disomy 16 and genetic counseling: new case and survey of published cases

Uniparental disomy (UPD) is the occurrence of both homologous chromosomes from one parent. Maternal UPD(16) is the most often reported UPD other than UPD(15); almost all cases are associated with confined placental mosaicism (CPM). Most of maternal UPD(16) cases are characterised by intrauterine growth retardation (IUGR) and different congenital malformations. Maternal UPD(16) has therefore been suspected to have clinical effects: however, the lack of uniqueness and specificity of the birth defects observed suggests that the phenotype may be related in parts to placental insufficiency. We report on a new case of maternal UPD(16) associated with low level trisomy 16 mosaicism in placenta and fetus. IUGR was noticed at 19 gestational weeks and the fetus died intrauterine. Apart from different craniofacial dysmorphisms she showed anal atresia. While IUGR is probably associated with trisomy 16 mosaicism, anal atresia is more characteristic for maternal UPD( 16). Considering the features in our patient as well as those in maternal UPD (16) cases from the literature, indications for UPD (16) testing can be defined: They include trisomy 16 mosaicism, IUGR and congenital anomalies (anal atresia, congenital heart defects). However, there is an overlap of clinical signs in mosaic trisomy 16 cases mosaic for maternal UPD(16) as opposed to those mosaic for biparental disomy 16. The management of trisomy 16 pregnancies should not differ from those in which maternal UPD(16) is confirmed. Therefore, a prenatal testing for UPD(16) is not useful, but it should be offered postnatally. The molecular genetic proof of maternal UPD(16) excludes an increased recurrence risk for the family for further pregnancies.     

Proliferation enhancement by spontaneous multiplication of chromosome 7 in rheumatic synovial cells in vitro

Mosaic trisomy of chromosome 7 is known to occur in a variety of non-neoplastic hyperproliferative disorders. In long-term cell cultures established from rheumatic synovium with mosaic trisomy 7, we observed a continuous increase in the proportion of cells with trisomy 7 to over 50% by the 10th in vitro passage. Simultaneous in situ hybridization with a repetitive chromosome-7-specific DNA probe and fluorescent Ki-67 labelling showed a strong correlation between trisomy 7 and an elevated proliferation index in cultured rheumatic synovial cells. Moreover, we observed a fraction of rapidly proliferating cells with up to eight copies of chromosome 7 as the sole cytogenetic change. Frequent somatic pairing of centromeres of two chromosomes 7 in interphase nuclei suggests either atypical non-disjunction with a persisting centromere or selective endoreduplication of chromosome 7.