Perinatal mortality and XY/XX mosaicism

Summary An XX/XY mosaicism was detected in two phenotypically male newborns with perinatal death. The importance of chromosome studies at the paediatric necropsy and the significance of the present findings are discussed.     

A phenotypically normal liveborn male after prenatal diagnosis of trisomy 20 mosaicism

We report on a case of prenatally diagnosed true trisomy 20 mosaicism in amniocytes. Cytogenetic analysis was performed postnatally on lymphocytes and extra-embryonic tissues. For analysing uroepithelial cells we established a new cell nuclei preparation protocol for FISH (Fluorescence In Situ Hybridization). Trisomy 20 cells could not be confirmed after birth. The origin or trisomy 20 cells in amniotic fluid remains unclear. The phenotypically normal male baby is developing normal.     

Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.     

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.     

Confined chorionic mosaicism in prenatal diagnosis

Summary Confined chorionic mosaicism, detected commonly on chorionic villus sampling (CVS) and occasionally in cultured amniotic fluid cells, is described in five pregnancies that showed confined chorionic mosaicism for trisomies 12, 13, 14, 17 and a marker chromosome. Cytogenetic findings in these pregnancies support the conclusion that within chorion some chromosomal mosaicism are confined to the trophectoderm derivatives while others to the extra-embryonic mesoderm. The etiology of confined chorionic mosaicism is discussed in relation to a significant role of multiple cell lineages contributing to the early development of placenta. The need is indicated for the use of both direct and long-term cultures in CVS prenatal diagnosis, and for the confirmatory testing of fetal blood or amniotic fluid in cases where mosaicism is detected in chorionic villi.     

Exclusion of chromosomal mosaicism in prenatal diagnosis

Summary For use in prenatal diagnosis, tables were prepared giving the number of metaphases or clones, respectively, which must be analysed in order to detect fetal mosaicism of a given degree (=percentage of the aberrant cell population) or higher with at least 95% or 99% probability. Different tables are provided for the two techniques of chromosomal preparation: the colony method and the flask method.     

A case of true hermaphroditism with 45X/46XY mosaicism

Summary The authors describe a case of true hermaphroditism of mainly female phenotype, ambiguous external genitalia, and ovotestis. The cytogenetic studies revealed 45X/46XY mosaicism and an absence of Barr bodies.     

46,XX/46,XX,del (10) (p13)/47,XX,+r/47,XX,del (10) (p13), + r mosaicism and partial trisomy 10p phenotype (author's transl)]

The mosaicism 46,XX/46,XX,del(10)(p13)/47,XX, +r/47,XX,del(10)(p13), +r was found in the lymphocytes and the fibroblasts of a patient with the following : profound mental retardation; craniofacial dysmorphism with frontal bossing, fine eyebrows, a large hypoplastic nasal bridge, prognathism of the upper jaw, thick lips; a long and thin neck; congenital heart disease; skeletal malformations, with club feet; and hypotonia and lax ligaments. These malformations, compatible with the trisomy 10p syndrome, suggest that the supernumerary ring chromosome was composed of 10p material. An increase of HK1 and GOT1 activities was found. This is in favour of a partial trisomy of chromosome 10. The relative frequencies of the clones constituting the mosaic vary from tissue to tissue and with time.     

Prenatally identified case of mosaicism of chromosome 16 trisomy

We present the prenatally identified case of mosaicism of chromosome 16 trisomy. A patient with the pregnancy complicated in the first trimester by the threat of breaking was refered to the high risk group according to the results of the screening program. The ultrasonic research revealed a number of phenotypical pathologies in 19-weeks-old fetus such as congenital heart disease (ventricular septal defect), hyperechoic bowel, single umbilical artery and some other ones. Cytogenetical and FISH analyses of the placental villi revealed karyotype with chromosome 16 trisomy. The further research of amniotic fluid cells revealed the karyotype of fetus as mos47,XX,+16 / 46,XX. The pathologoanatomic research of the abortus has verified the multiple congenital malformations.     

A case of trisomy 18 mosaicism with peculiar features

Summary A new case of 46XX/47XX 18+mosaicism is presented and the clinical findings of this type of mosaicism are discussed with particular emphasis on congenital asymmetry and elevation of sweat chlorides.

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Zusammenfassung Chromosomale Mosaiken 46/47, 18+sind sehr selten; nur acht solche Fälle sind bisher beobachtet worden. Ein neunter Fall wird in der vorliegenden Arbeit beschrieben. Die Symptomatologie dieser Chromosomenanomalie — derjenigen der Trisomie 18 sehr ähnlich — wird besprochen, wobei besonders darauf hingewiesen wird, daß der Patient leicht erhöhte Chloride im Schweiß und eine auffallende Körperasymmetrie aufwies. Körperasymmetrien sind schon mehrfach bei 46/47, 18+Mosaik beobachtet worden. Eine kausale Beziehung zwischen dieser Chromosomenanomalie und der Körperasymmetrie wird diskutiert.

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Supplemented by a fellowship of NATO (Dr. L. Pavone) and a Special Project Budget MR 12, HEW, Children's Bureau, Clinical Research in Mental Retardation and Genetic Study.     

A case of 46,XY/45,X/46,XX intersex

Summary A case of 46,XY/45,X/46,XX mosaicism in a phenotypic intersex is decribed in detail. A few relevant aspects, which emerge especially from the phenotypic and karyotypic analysis, are briefly commented upon.

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Zusammenfassung Es wird ein Fall von Mosaicismus 46,XY/45,X/46,XX beschrieben. Einige Aspekte, die aus der phänotypischen und karyotypischen Analyse des Patienten hervorgehen, sind kurz kommentiert.

     

45, X/47, XY, +13 mosaicism in a 19-year-old girl]

The 45, X/47, XY, +13 mosaicism was observed in a 19-year-old mentally deficient girl who was examined because of primary amenorrhea. Certain clinical features were reminiscent of Turner's syndrome, while no features of trisomy 13 were present. The study of blood groups, HLA genotypes, and cytogenetic markers provided no evidence of chimerism.     

XO/XY mosaicism and non-fluorescing Y chromosome in a male

Summary An adult male of short stature and with underdeveloped external genitalia is described, who carried out a number of sexual assaults on young women. He proved to have XO/XY mosaicism and a non-fluorescing Y chromosome. It was considered to be a terminal deletion on morphological grounds. It is suggested, on the evidence of the small number of XO/XY mosaics examined by appropriate staining methods, that an abnormal Y chromosome, whether terminally deleted or non-fluorescing owing to an altered chemical state, predisposes to anaphase lagging and non-disjunction.Of eleven reported cases of XO/XY mosaicism with a non-fluorescing Y chromosome, this is the fifth of male phenotype. The severe behaviour disturbance of early onset is considered to be probably causally associated with the chromosome anomaly.     

X/XY/XYY mosaicism as a cause of subfertility in boars: a single case study

Sex chromosome abnormalities are common in mammals and humans and are often associated with subfertility. In this study a boar with normal sperm parameters was indicated to have reduced prolificacy from figures obtained for return rate, farrowing rate and total number of piglets born. G-banded cytogenetic analysis of peripheral blood identified an abnormal mosaic sex chromosome constitution 39,XYY[74]/38,XY[23]/37,X[3]. Cytogenetic analysis of fibroblasts confirmed this mosaic karyotype with similar percentages of cell lines observed 39,XYY[76]/38,XY[19]/37,X[5]. External genitalia revealed a poorly developed scrotum with the right testicle being smaller than the left. To the best of our knowledge this is the first time that this chromosome constitution has been reported in the pig. It is of particular interest that this karyotype is associated with reduced boar fertility, which could lead to potential economic losses if such a boar were selected for breeding purposes.     

Demonstration of spontaneous XX/XY chimerism by DNA fingerprinting

Summary The M13 bacteriophage probe, which makes possible the establishment of DNA fingerprints, was used to study a phenotypically normal woman with a 46XY karyotype and her twin brother. Identical fingerprints and positive hybridzation with a series of Y-specific probes were obtained on blood samples from the siblings. DNA from a skin biopsy of the woman yielded a clearly different pattern and displayed no Y-specific hybridization, indicating that she is a spontaneous chimera. This study illustrates the use of DNA fingerprinting as a powerful and simple aid to the diagnosis of natural chimerism.     

The reproductive performance of XX/XY male chimeric mice

The reproductive performance of male aggregation chimeric mice was examined. C57BL/6 in equilibrium BALB/c male chimeras and control animals, C57BL/6, BALB/c, and their reciprocal F1 crosses, were mated with ICR females. Of 45 overt chimeras, 13 produced mixed-genotype progenies and were revealed to be XY/XY chimeras. By karyotype analysis 16 of 32 single-genotype progeny chimeras were determined to be XX/XY chimeras, but the remaining single-genotype progeny chimeras showed only XY metaphase plates, so that their chromosomal sex could not be determined. The mean litter size of C57BL/6 was significantly higher than that of BALB/c. In contrast, the birth rate of C57BL/6 was lower than that of BALB/c. XY/XY chimeras showed almost the same performance as C57BL/6 for litter size and as BALB/c for birth rate. There were no significant differences for both traits between the reciprocal F1 crosses and XY/XY chimeras. The mean litter size of XX/XY chimeras was lower than that of XY/XY chimeras and the differences was statistically significant. Some XX/XY chimeras had very small testes, while XY/XY chimeras had normal testes. Such results indicate that the reproductive performance of XX/XY male chimeras is inferior to that of XY/XY males.     

Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis

To investigate the incidence and clinical significance of chromosomal mosaicism (CM) in prenatal diagnosis by G-banding karyotyping and chromosomal microarray analysis (CMA). This is a single-centre retrospective study of invasive prenatal diagnosis for CM. From 5758 karyotyping results and 6066 CMA results, 104 foetal cases with CM were selected and analysed further. In total, 50% (52/104) of foetal cases with CM were affected by ultrasound-detectable phenotypes. Regardless of whether they were singleton or twin pregnancies, isolated structural defects in one system (51.35%, 19/37 in singletons; 86.67%, 13/15 in twins) and a single soft marker (18.92%, 7/37 in singletons; 13.33%, 2/15 in twins) were the most common ultrasound anomalies. Mosaic autosomal trisomy (19.23%, 20/104) was the most frequent type, and its rate was higher in phenotypic foetuses (28.85%, 15/52) than in non-phenotypic foetuses (9.62%, 5/52). There was no difference in mosaic fractions between phenotypic and non-phenotypic foetuses based on specimen sources or overall classification. Discordant mosaic results were observed in 16 cases (15.38%, 16/104) from different specimens or different testing methods. Genetic counselling and clinical management regarding CM in prenatal diagnosis remain challenging due to the variable phenotypes and unclear significance. Greater caution should be used in prenatal counselling, and more comprehensive assays involving serial ultrasound examinations, different specimens or testing methods verifications and follow-up should be applied.     

XO/XY mosaicism in a 2 year phenotypic male.

A 2-year-old male with bilateral undescended gonads, hypoplastic external auditory canals, large umbilical hernia and XO/XY chromosome mosaicism is described in this communication. Salient features of other similar cases, i.e. XO/XY mosaicism in phenotypic males, from the literature are summarized, showing the wide diversity of manifestations of this syndrome.