Mosaic trisomy 12 is a rare genetic condition with a highly variable phenotype.Clinical features associated with this condition include developmental delay,intellectual disabil-ity,dysmorphic facial features,short stature,pigmentary dysplasia,complex congenital heart defects and hypotonia(Table 1).To date,20 patients have been described in which mosaic trisomy 12 was observed in both extraembryonic and neonatal/infant tissues.Chen et al.reported two cases without phenotypic abnormalities [1].Of the 20 previously reported cases,4 resulted in neonatal or infant death.Those findings support the hypothesis that mosaic trisomy 12 man-ifests across a wide spectrum of phenotypes and that predict-ing the degree of abnormalities is quite difficult [2-4].In several cases,trisomy 12 mosaicism was detected prenatally in amnion fluid,but not postnatally [5-8].Even if the mosai-cism is not confirmed in one tissue,it may still be present in other tissues of the child.

Constitutional ring chromosomes can be found for all human chromosomes and are very rare chromosomal abnormalities. A complete ring chromosome without loss of genetic material results from fusion of subtelomeric regions or telomere–telomere fusion. In cases of complete ring chromosome, an increased incidence of severe growth failure with no or only minor anomalies has been observed and attributed to ring syndrome. Ring syndrome is thought to be caused by “dynamic mosaicism” due to ring instability. We report a 6‐year‐old boy with de novo ring chromosome 4 and typical characteristics of the ring syndrome, namely, proportionate severe growth failure, microcephaly, and minor anomalies. Cytogenetic studies showed complete ring chromosome 4 with mitotic instability. Microarray gave normal results, thus excluding the loss of detectable genetic material. The literature of complete ring chromosome 4 is reviewed. Our case report supports the theory of ring syndrome. No studies about the effects and possible side effects of growth hormone therapy on patients with ring chromosomes have yet been published. We suggest that cytogenetic monitoring of the rate of secondary aberrations in patients with ring chromosome undergoing growth hormone therapy might be feasible. Since the diagnosis would have been missed by molecular karyotyping, our case report underlines the continuing role of classical cytogenetics for the evaluation of structural chromosomal abnormalities in patients with mental and/or physical anomalies. Standard karyotyping is still indispensable and should have an ongoing role as first‐tier analysis together with molecular karyotyping. © 2017 Wiley Periodicals, Inc.

Poster Abstracts1. Clinical Cytogenetics1.P80 Subtelomere fluorescence in situ hybridization as a powerful tool to screen for submicroscopic balanced rearrangements in couples with recurred abortions/stillbirth despite of the era of exome sequencingIlona Dietze-Armana1, Barbara Fritz2, Karl Mehnert3 1Cytogenetic genetikum Neu, Ulm, Germany; 2Clinical Genetics Philipps, University Marburg Germany; 3Genetic Counselling/Cytogenetic genetikum Neu, Ulm, Germany Correspondence: Ilona Dietze-ArmanaCryptic terminal chromosomal rearrangements are known to cause human genetic diseases. They are mostly undetectable by conventional chromosome analysis even of the highest resolution. Subtelomere fluorescence in situ hybridisation (FISH) analysis has increasingly been used as an adjunct to routine cytogenetic testing in order to detect small rearrangements. Indications for this application are: 1) conspicuous familial medical history, 2) ultrasound abnormalities in a previous pregnancy, 3) late abortion/IUFT/still birth.Here we present four couples with remarkable medical history. We found in a mother, (case 1), with ultrasound abnormalities in two fetuses, a 10q/11p subtelomeric cryptic reciprocal translocation (crt). In the fifth abortion of a woman (case 2) we found a paternally inherited unbalanced form of the 8q/11q translocation detected by array-CGH. In case 3, a mother, who had a stillbirth at 28 weeks of gestation, a crt 6q/8q was found. Furthermore, a 1q/16p crt was seen in a man whose partner had recurrent abortions (case 4).The clinical information including the family history of these patients will be summarized and compared with the current literature.We propose the use of subtelomere FISH as a reliable, rapid and economical first approach to detect unbalanced terminal chromosomal rearrangements, especially in absence of major chromosome rearrangements in routine diagnosis. Detailed analysis of the family history helps to choose further methods of more diagnostic power.1.P81 The role of classical cytogenetics for detection of autosomal structural changes after birth in the Romanian populationMariela Sanda Militaru1, Mihai Militaru2, Alexandra Maris3, Maria Stefanut4, Iulia Blanaru4, Diana Militaru5, Eleonora Dronca1 1UMF Iuliu Hatieganu Medical Genetics Cluj, Napoca, Romania; 2UMF Iuliu Hatieganu Pediatrics no.2 Cluj, Napoca, Romania; 3Children's Hospital Intensive care unit Cluj, Napoca, Romania; 4Genetic Center Genetics Cluj, Napoca, Romania; 5Faculty of Medicine Student Oradea, Romania Correspondence: Mariela Sanda Militaru Introduction Chromosome abnormalities account for 50% of all spontaneous miscarriages and are present in 0,5-1% of all newborn infants.The present study was undertaken to investigate the different types of structural chromosomal aberrations and their relative frequencies in a group of patients with suspected genetic disorders in the Romanian population, and to identify precisely the role of cytogenetic investigation in confirming the diagnosis, thus allowing proper genetic counseling. Material and Methods We cytogenetically investigated a total of 927 patients using the G banding technique for identifying and characterizing the chromosomes of lymphocytes. Results We identified a total of 121 chromosomal aberrations (13%), of which 83 were numerical abnormalities (8.9%) and 38 were structural abnormalities (4.1%). Of the 38 structural abnormalities, 28 were autosomal chromosomal abnormalities. Changes in chromosome structure encountered were: different translocations-11 cases, deletions-7 cases, inversions-5 cases, 3 cases chromosomal polymorphisms, and 2 cases of marker chromosomes. Conclusions Detection of structural chromosomal abnormalities is a key element for both correct etiological diagnosis and genetic counseling. The results are comparable to those of similar studies.1.P82 A case of Rothmund-Thomson syndrome without mosaic trisomy 8, but with structural chromosome instabilityStefan Müller1, Ilona Kutschka1, Yasmin Mehraein1, Luana Niculescu2, Kathrin Giehl2, Ortrud Steinlein1 1Ludwig-Maximilians-University Munich Institute of Human Genetics, University Hospital Munich, Germany; 2Ludwig-Maximilians-University Munich Department of Dermatology, University Hospital Munich, Germany Correspondence: Stefan MüllerRothmund-Thomson syndrome (RTS) is a rare autosomal recessively transmitted genodermatosis associated with congenital bone defects and increased risk of osteosarcoma and skin cancer. RTS is caused by homozygous or compound heterozygous RECQL4 mutations. RecQ helicases are implicated in damaged DNA replication fork repair and are assumed to play roles in the maintenance of genome stability.Some previous cytogenetic studies described mosaic trisomy 8 in RTS patients, an intriguing finding because RECQL4 is located on 8q24.3. However, it is unknown if these findings point towards a causal association because the functional implications would be difficult to explain. To address this question, we performed a blinded, unbiased interphase FISH screen for copy number changes of all chromosomes and M-FISH karyotyped more than 200 metaphases from a RTS patient.Our interphase FISH analysis provided no evidence for a general increase in aneuploidy, and specifically no trisomy 8 rates above the cut-off (P < =0.005) were observed. In contrast, M-FISH karyotyping revealed a 2.7% translocation rate in our patient, representing a significant and up to 5.7x increase compared to baseline frequencies in healthy age matched controls from the literature.We conclude that aneuploidy, and in particular mosaic trisomy 8 is not an apparent pathogenic mechanism in the RTS patient we have analysed. However, and in line with the proposed function of RECQL4 in DNA replication and genome surveillance, we found evidence that increased structural genome instability might be associated with the RTS phenotype.2. Tumour Cytogenetics2.P42 Clinical and biological significance of Y chromosome loss in a series of 2,423 male patients with Myelodysplastic syndromes and Chronic Myelomonocytic LeukemiaDolors Costa1, Meritxell Nomdedeu2, Arturo Pereira3, Xavier Calvo4, Joan Colomer1, Francesc Soler5, Elisa Luño6, Jose Cervera7, Amparo Arias1, Cándida Gómez1, Magui Ortega8, Rosa Collado9, Isabel Granada10, Guillermo Sanz7, Jordi Esteve3, Elias Campo1 1Hospital Clínic Unitat D'hematopatologia Barcelona, Spain; 2Hospital Plató Hematologia Barcelona, Spain; 3Hospital Clínic Hematologia Barcelona, Spain; 4Hospital del Mar Hematologia Barcelona, Spain; 5Hospital Trias I Pujol Josep Carreras Leukemia Research Institute Badalona, Spain; 6Hospital Central de Asturias Hematologia Oviedo, Spain; 7Hospital La Fe Hematologia Valencia, Spain; 8Hospital Vall D'hebron Hematologia Barcelona, Spain; 9Hospital General Hematologia Valencia, Spain; 10Hospital Trias I Pujol Hematologia Badalona, Spain Correspondence: Dolors CostaIsolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases with isolated -Y, and test whether finding -Y may predispose to over-diagnose MDS in patients with borderline morphological features. We evaluated 3,581 male patients from the Spanish MDS Registry with a diagnosis of MDS or chronic myelomonocytic leukemia (CMML). -Y was identified in 177 patients (4.9%). Compared with the 2,246 male patients with normal karyotype, -Y group showed a reduced risk of leukemic transformation that did not translate into a survival advantage. The overall survival and the risk of leukemic transformation were not influenced by the percentage of metaphases with -Y. The -Y group was not enriched in patients with minor morphologic traits of dysplasia, suggesting that the better outcome in the -Y group cannot be explained by enrichment in cases misdiagnosed as MDS. In conclusion, our results support the current recommendation of classifying patients with -Y within the very good risk category of the IPSS-R for MDS and rule out a selection bias as a possible explanation of this better outcome. An analysis of the molecular basis of MDS with isolated -Y would be of interest as it may provide a biological basis of protection against progression to acute leukemia.

Small supernumerary marker chromosomes (sSMC) are known for being present in mosaic form as 47,+mar/46 in >50% of the cases with this kind of extra chromosomes. However, no detailed studies have been done for the mitotic stability of sSMC so far, mainly due to the lack of a corresponding in vitro model system. Recently, we established an sSMC-cell bank (Else Kröner-Fresenius-sSMC-cellbank) with >150 cell lines. Therefore, 93 selected sSMC cases were studied here for the presence of the corresponding marker chromosomes before and after Epstein-Barr virus-induced immortalization. The obtained results showed that dicentric inverted duplicated-shaped sSMC are by far more stable in vitro than monocentric centric minute- or ring-shaped sSMC. Simultaneously, a review of the literature revealed that a comparable shape-dependent mitotic stability can be found in vivo in sSMC carriers. Additionally, a possible impact of the age of the sSMC carrier on mitotic stability was found: sSMC cell lines established from patients between 10-20 years of age were predominantly mitotically unstable. The latter finding was independent of the sSMC shape. The present study shows that in vitro models can lead to new and exciting insights into the biology of this genetically and clinically heterogeneous patient group.