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Objectives: To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories. Methods: Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non-invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed. Results: Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs. PPVs for T21, T18, and T13 were significantly higher when diagnostic confirmation was carried out on chorionic villi (97.5%) compared to amniotic fluid (89.5%) (p < 0.001). In 19/139 (13.9%), of no result cases, a cytogenetic abnormality was detected. Follow-up genetic testing provided explanations for 3/6 cases with a fetal sex discordancy between NIPT and ultrasound. Conclusions: NIPT PPVs differ across the conditions screened and the tissues studied in diagnostic testing. This variability, issues associated with fetal sex discordancy, and no results, illustrate the importance of pre- and post-test counselling.

The ancestral platyrrhine karyotype was characterised by a syntenic association of human 5 and a small segment of human 7 orthologues. This large syntenic association has undergone numerous rearrangements in various phylogenetic lines. We used a locus-specific molecular cytogenetic approach to study the chromosomal evolution of the human 7q11.23 orthologous sequences (William-Beuren syndrome, WS) in various Ceboidea (Platyrrhini) species. The fluorescent in situ hybridisation of the WS probe revealed a two-way pattern of chromosomal organisation that suggests various evolutionary scenarios. The first pattern (seen in Callimico and Saimiri ) includes a fairly simple disruption of the 7/5 syntenic association by a chromosome fission. The second pattern (seen in Atelinae, Alouattinae and in Callicebus ) is characterised by an increasing complexity in the 7/5 association as a consequence of a series of inversions and translocations resulting in different syntenic associations. These data support recent proposals for phylogenomic groupings of New World monkeys. The study also illustrates how single-locus probe hybridisations can reveal intrachromosomal rearrangements.

Transabdominal chorionic villus sampling (TA-CVS) was attempted in 328 high-risk pregnancies at 6-7 weeks of gestation. Sampling was feasible in 97.7 per cent of cases; chorionic tissue specimens of more than 10 mg were obtained in 94.4 per cent of cases at the first needle insertion and in 100 per cent after a second attempt. Fetal karyotyping succeeded in 99.4 per cent of cases, while no diagnostic failures were reported in enzymatic and DNA analyses. Fetal loss rate in the first 4 weeks after CVS was significantly higher than in the later CVS series (7.2 vs. 2.5 per cent), but 50 per cent of losses were observed within 2 weeks in cases of inviable aneuploidies. A high incidence of severe limb abnormalities (1.6 per cent) was detected in pregnancies intended to continue, confirming the aetiological role of early CVS. Unclear visualization of the placental limits and poor control of the needle path are thought to be the main reasons for the vascular disruption of the chorionic plate, and thereby hypoxic embryo tissue damage. A better selection of cases, together with high-resolution vaginal ultrasound visualization, and analytical techniques requiring a minimal amount of tissue should avoid any teratogenic effect of early CVS.

Human chromosome 7 has a complex syntenic origin. It was divided into two segments in both the ancestral primate karyotype and in Platyrrhini. Apparently, a small segment in the ancestral platyrrhine karyotype was associated with HSA5 and the remainder formed a middle-sized submetacentric. We tested the dynamics of platyrrhine chromosomes by hybridizing the locus specific Willams-Beuren probe (7q 11.23, 450 kb) to chromosomes of representative species from the three families of the New World monkeys recently proposed by molecular genomics: Cebidae, Callithrix argentata (bare ear marmoset or silvery marmoset, 2n = 44); Pitheciidae, Callicebus cupreus [red titi monkey, or coppery monkey, 2n = 46)] and Atelidae, Alouatta caraya (black and gold howler, 2n = 52). In both the marmoset and the howler monkeys, the signal was found on the small segment of chromosome 7 associated with human chromosome 5, but not in Callicebus cupreus. Instead, the Williams-Beuren syndrome (WS) signal was found on a C. cupreus chromosome previously reported to be hybridized only by human chromosome 1. The WS probe indicates a small, but complex translocation never described before. Our results point out that fluorescence in situ hybridization (FISH) with locus specific probes and cloned DNA fragments such as bacterial aftificial chromosomes (BACs) provides higher resolution than FISH with whole chromosomes paints. It may be well that the variability seen in the hybridization patterns and revealed by the WS FISH in this report is as a result of a rearrangement ‘hot spot’. The WS region in humans is composed of region-specific different blocks of complex segmental duplications that probably promote the extraordinary rate of evolutionary dynamics of this region among primate species, and which continues to be reflected today by the predisposition of this region to disease syndromes such as WS. The evolutionary history of this region also suggests that repeat families in this region had their origin in a common ancestor of both Old World and New World monkeys. Resumen El mapeo de la Sonda Williams-Beuren Sobre Callithrix Argentata, Callicebus Cupreus y Alouatta Caraya Revela un Diferente Pattern de Los Desplazamientos Genomicos en Los Monos del Nuevo Mundo La tecnica del Mapeo de la sonda Williams-Beuren sobre Callithrix argentata, Callicebus cupreus y Alouatta caraya revela un diferente ‘pattern’ de los desplazamientos genomicos en los Monos del Nuevo Mundo El cromosoma humano 7 tiene un origen syntenico complejo. En el cariotipo ancestral de los Primates y en Platyrrhini viventes se encontra en dos segmentos; el pequeno en Platyrrhine se asocia al cromosoma humano 5 y el resto forma un cromosoma submetacentrico de tamano mediano. Se ha probado la dinamica de los cromosomas de los Monos del Nuevo Mundo ibridando la sonda especifica de William-Beuren (7q 11.23, 450 kb) sobre los cromosomas de algunas especies representativas de las tres familias Platyrrhini: Cebidae, Callithrix argentata (2n = 44); Pitheciidae, Callicebus cupreus (Groves 1992, 2n = 46), y Atelidae, Alouatta caraya (2n = 52). Esta clasificacion ha sido propuesta recientemente a traves de la realizacion de estudios de genetica molecular. En todas las especies analizadas la senal se ha encontrado en el segmento pequeno del cromosoma 7 que esta asociado al cromosoma humano 5, excepto en el Callicebus cupreus, en la cual, la senal de la sonda William-Beuren ha sido encontrada en otro cromosoma distinto que se ibrida normalmente con el cromosoma humano 1. La sonda William-Beuren indica, por lo tanto, un desplazamiento pequeno, pero complejo, nunca descrito antes. Estos resultados revelan que la tecnica de mapeo locus especifica tiene una resolucion mayor que la FISH hecha con las sondas ‘painting’. Los cambios genomicos que se han podido observar gracias a la tecnica FISH se pueden explicar teniendo en cuenta la existencia de puntos calientes –‘hotspot’ en el genoma. La region de la sonda William-Beuren en el cromosoma 7 humano esta formada por distintos bloques complejos de segmentos de duplicacion que son con probabilidad responsables de este elevado grado de dinamismo evolutivo entre especies de primates; predisposition que en esta region se refleja hoy en el sindrome William-Beuren. Por ultimo, la historia evolutiva de esta region sugiere que los bloques de duplication tengon su origen en un antepasado comun a los Monos del Viejo Mundo y de Nuevo Mundo.

Background We report on a fetus with sex reversal and del(9)(p24) consequent to a malsegregation of a maternal balanced complex translocation involving chromosomes 7, 9 and 11. Methods Fluorescence in situ hybridization (FISH) was performed in order to verify the presence of the SRY gene and the absence of DMRT1 and DMRT2 genes located in 9p24.3 region and frequently associated with sex reversal. Results and Conclusions The prenatal karyotype revealed an unbalanced male fetus. The postmortem examination showed a malformed fetus with female external genitalia. Lack of DMRT1-2 genes established by FISH. Copyright © 2005 John Wiley & Sons, Ltd.