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Study question Influence of sperm selector separation of sperms on their translocation load, segregation pattern, motility and occurrence of interchromosomal effects Summary answer Sperm selector separation led to reduction of the translocation load, shift in segregation pattern and lower rates of interchromosomal effects within sperm samples What is known already Balanced translocations in men are known to be one of the main causes of reproductive failure. The segregation pattern in sperms is determined by the distribution of the chromosomes during meiosis. Interchromosomal effects can also influence the distribution of chromosomes that are not involved in the translocation. The sperm selector used consists of two concentric chambers, which are overlaid by a U-ring and a cover glass. Motile sperms migrate from the native ejaculate in the medium filled inner chamber by using a capillary bridge created by the U-ring. This avoids potential harmful centrifugation and allows accumulation of motile sperms. Study design, size, duration Twenty-one carriers of balanced translocations participated in the study. In addition, 15 patients were involved as control. All participants signed an informed consent (F–8–15). Samples of three patients did not meet the internal quality criteria and had to be excluded from analysis. The study started in 2015 and is still ongoing. Participants/materials, setting, methods Liquefied native ejaculate was processed with a sperm selector. Native ejaculate, non-migrated sperms from the outer chamber and migrated sperms from the inner chamber were transferred onto glass slides, fixed and underwent a decondensation treatment. For segregation analysis FISH translocation specific FISH probe mixes were used and tested on patient’s blood. Interchromosomal effects were analysed with FISH probes for the chromosomes X, Y, 18 and 13, 21. Evaluation was done manually using fluorescence microscopy. Main results and the role of chance Segregation analysis was done for more than 25,000 sperms from men carrying a balanced translocation (18 patients with reciprocal and 3 patients with Robertsonian translocation). Separation via sperm selector led to a reduction in translocation load (native to separated approach 49,1±11,5% to 34,8±9,4% (P = Limitations, reasons for caution The number of accumulated strandbreak-free sperms depended on the motility and sperm count of the native ejaculate. Examinations are not reproducible, as each sample delivery is influenced by external circumstances Wider implications of the findings: Sperm selector separation can be used before ART to reduce the translocation load and rate of maldistribution in sperms from carriers of balanced translocations. This could have a considerable impact on PGT results after trophectoderm biops. Trial registration number Not applicable

Mehr als in anderen Fachgebieten gehoren angeborene Erkrankungen zum Alltag des Facharztes fur Kinder- und Jugendmedizin. Die zunehmende Verfugbarkeit der Next Generation Sequencing-Methoden in den letzten 5 Jahren zeigt, dass die meisten dieser Erkrankungen genetischen bzw. monogenen Ursprungs sind, und eroffnet ungeahnte Moglichkeiten, aber auch Herausforderungen in Diagnostik und Therapie. Dieser Beitrag bietet einen Uberblick uber die Bedeutung genetischer Erkrankungen in der Padiatrie, erlautert die Moglichkeiten, aber auch Limitationen moderner genetischer Diagnostik wie der Exomsequenzierung und ihre Auswirkungen auf die tagliche Patientenversorgung.

Introduction Sexually transmitted infections (STIs) continue to be a significant public health problem with a high burden in women of reproductive age. Rates of Chlamydia trachomatis , Neisseria gonorrhoeae and Trichomonas vaginalis are frequently tested for and rates of infection are generally high in African settings, but the prevalence of other genital STIs is largely unknown. The aim of this study was to determine the prevalence of genital mycoplasmas ( Mycoplasma genitalium , M. hominis , Ureaplasma parvum and U. urealyticum ) in women visiting the infertility clinic of a tertiary academic hospital in South Africa. Methods In this pilot evaluation self-collected vaginal swabs were obtained from 51 women visiting the infertility clinic. The genomic DNA was extracted from the swabs using the ZR Fungal/Bacterial DNA Miniprep (Thermo Scientific, USA) and analysed using the Anyplex II STI-7 (Seegene, Korea) real-time PCR assay for the simultaneous detection and identification of seven STIs including the four mycoplasma species. Results The real-time PCR assay detected the following genital mycoplasmas and co-infections in the 51 women: U. parvum [55% (28/51)], M. hominis [20% (10/51)] and U. urealyticum [16% (8/51)]; none of the specimens tested positive for M. genitalium . Among the nine patients where mixed infections were observed, M. hominis and Ureaplasma spp. were frequently detected together [67% (6/9)]. In addition to the mycoplasmas, one woman tested positive for C. trachomatis; N. gonorrhoeae and T. vaginalis were not detected. Conclusion This pilot study demonstrated an unexpectedly high rate of genital mycoplasma infections among women visiting an infertility clinic. The burden of genital mycoplasma infection is largely unknown and warrants further investigation, in particular with regards to the prevalence and clinical significance in different population groups. Support: Anyplex II STI-7 kits provided by Seegene, Korea

A case of prenatal diagnosis of de novo mosaic deletion of the long arm of chromosome 13 (del(13)(q13.3)) is presented. Routine scanning in a 27-year-old primigravida at 25 weeks' gestation showed fetal bilateral hydronephrosis. Detailed anomaly scanning in our tertiary referral center further demonstrated posterior meningoencephalocele, sloping forehead, microcephaly, syndactyly and hypoplastic thumbs. Both genetic amniocentesis and cordocentesis revealed a mosaic karyotype, 46,XY/46,XY,del(13)(q13.3). Sonographic findings were confirmed by postmortem autopsy and additional abnormalities such as agenesis of corpus callosum, hypoplastic cerebellum and macroglossia were diagnosed. Detailed sonography in this case thus revealed multiple malformations that prompted fetal karyotyping at 25 weeks' gestation.

Background and aims Germline mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer (HDGC). These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance. We describe the clinical presentation of three sibling cases with advanced gastric cancer, the way of confirming the suspicion of underlying HDGC and the clinical management of the other healthy family members. Methods Screening for CDH1 germline mutation was carried out by denaturing high-performance liquid chromatography and automated DNA sequencing. The clinical suspicion of HDGC has been confirmed by identifying a frameshift mutation in exon 9 (1302_1303insA, 1306_1307delTT) of the E-cadherin gene. Results Eight of nine tested family members were positive for the CDH1 germline mutation. Prophylactic laparoscopic gastrectomies were performed in five mutation carriers. After pathological examination, we could identify intramucosal malignant signet-ring cell carcinoma in all resected stomachs. Conclusion This report underlines that prophylactic gastrectomy remains the only option to eliminate the high risk for gastric cancer in CDH1 mutation carriers.

In 1988, a 27-year-old male patient received an allogeneic BMT for leukemic relapse 8 months after ABMT for AML (M2) in first complete remission. Because of chronic GVHD of the liver CsA was administered until 1994. Nine months after discontinuation of CsA, locally advanced gastric granulocytic sarcoma (GS) was diagnosed without evidence of systemic relapse. The patient was treated with two courses of polychemotherapy (ICE, NOVIA). Granulocyte colony-stimulating factor (G-CSF)-mobilized donor buffy coat cells were reinfused after each chemotherapy cycle in an attempt to accelerate hematopoietic regeneration and to induce a graft-versus-leukemia (GVL) effect. Local irradiation and surgical resection of residual leukemic cells resulted in complete remission. Seventeen months from diagnosis of GS the patient relapsed again with multiple lesions and died of generalized bleeding during aplasia after a third course of polychemotherapy (ICE). In our patient donor peripheral blood stem cell support did not accelerate hematopoietic regeneration (time to neutrophil recovery > 0.5 x 10(9) g/l from the start of chemotherapy was 27 days after ICE and 36 days after NOVIA) and did not result in long-term disease-free survival.

In 1963 Berg described lipoprotein (a) as a genetic variant of the low-density lipoprotein (LDL) and supposed it to be transmitted as an autosomal dominant trait [2]. Later investigators have shown that lipoprotein (a) represents a quantitative rather than a qualitative genetic marker, and that it is under polygenic control probably with a major gene effect for high concentrations [9, 10, 15]. As early as 1967 Renninger et al. [13] recognized a positive association with myocardial infarction. A series of subsequent investigations have confirmed and extended this observation [3, 11, 14]. Therefore it has been postulated that high concentrations of lipoprotein (a) in plasma represents an independent risk factor for the development of coronary heart disease.