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Non-invasive prenatal testing (NIPT) is currently the best screening test for fetal chromosome abnormalities with the highest sensitivity and specificity and can be done from 10 weeks gestation. We report a detection of 44.7 Mb duplication at 11p15.5-p11.2 by NIPT with a fetal fraction (FF) of only 3%. This chromosome abnormality was confirmed after amniocentesis by karyotyping and array comparative genomic hybridization (aCGH) on cultured fetal cells. Further parental investigation showed that the fetal chromosome abnormality was inherited from the mother who was a carrier of a balanced translocation 46,XX,t(11;X)(p11.2;q28). This case highlights the importance of expanded NIPT in the detection of fetal segmental aneuploidy. NIPT together with complementary studies can lead to the detection of parental chromosome rearrangement despite a low FF, which can impact the couple's reproductive plans. We also reviewed other cases with chromosome rearrangement, detected by NIPT, derived from a parental reciprocal translocation. [ABSTRACT FROM AUTHOR]

Abstract Background The ultraconserved elements (UCEs) are defined as stretches of at least 200 base pairs of human DNA that match identically with corresponding regions in the mouse and rat genomes, albeit their real significance remains an intriguing issue. These elements are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development. Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs). However no comprehensive survey of a putative enrichment of these elements among pathogenic dose variants has yet been reported. Results A survey for UCEs was performed among the 26 cryptic genomic rearrangements detected in our series of 200 patients with idiopathic neurodevelopmental disorders associated to congenital anomalies. A total of 29 elements, out of the 481 described UCEs, were contained in 13 of the 26 pathogenic gains or losses detected in our series, what represents a highly significant enrichment of ultraconserved elements. In addition, here we show that these elements are preferentially found in pathogenic deletions (enrichment ratio 3.6 vs. 0.5 in duplications), and that this association is not related with a higher content of genes. In contrast, pathogenic CNVs lacking UCEs showed almost a threefold higher content in genes. Conclusions We propose that these elements may be interpreted as hallmarks for dose-sensitive genes, particularly for those genes whose gain or loss may be directly implied in neurodevelopmental disorders. Therefore, their presence in genomic imbalances of unknown effect might be suggestive of a clinically relevant condition.

Ring chromosomes are circular structures formed as a result of breaks in the chromosome arms and the fusion of the proximal broken ends with a loss of distal material, or by fusion of dysfunctional telomeres without any loss. The mechanism underlying this process has not yet been sufficiently explained. Commonly, rings occur as acquired genetic abnormalities; however, sometimes they are found as constitutional aberrations with a prevalence of around 1:50,000 live births. Here, we present a new case of r(9) in a female fetus with intrauterine growth retardation and slight craniofacial dysmorphisms. Both parents had a normal phenotype. Amniotic fluid karyotype showed r(9)(p24q34). An array CGH revealed 3 deletion segments: a ring chromosome with a 2.57-Mb deletion at 9pterp24.2 (chr9:163,131-2,729,722), a 2.60-Mb deletion at 9q34.3qter (chr9:138,523,302-141,122,055), and also a 0.15-Mb interstitial deletion at 9p24.1 (chr9:5,090,443-5,235,765). These deletions overlap with proposed regions for the 9p24.3 deletion and Kleefstra syndrome. Segregation analysis revealed a maternal origin of the rearranged chromosome. We conclude that both the ring chromosome and the interstitial deletion occurred de novo. This last deletion has not been reported before. Prenatal array CGH, combined with fine mapping of breakpoints contributes to the assessment of genotype-phenotype correlations. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article discusses the inversion of the factor VIII gene (F8) causing haemophilia. According to initial hypothesis, homologous recombination between repeat int22h-1, in intron 22 of F8 and and one of the two duplicons, int22h-2 or int22h-3, in the reverse direction caused haemophilia A whereas at present, the duplicons are known to be inversely oriented in relation to each other forming imperfect palindrome with a central unique loop of 67.3 kb and arms of 50.5 kb.