Cell-free DNA Testing in Routine Practice: Characterisation of a Cohort with Positive Results for Trisomies, Sex Chromosome Anomalies and Microdeletions

Introduction Cell-free DNA (cfDNA) testing is increasingly used as a screening method not only for trisomy (T) 21 but also for T18 and T13, sex chromosome anomalies (SCA) and microdeletions. Based on cases with a positive cfDNA result in our specialised prenatal practice, this study aims to characterise the usage of cfDNA testing and to estimate the positive predictive value (PPV) in routine practice in Germany. Patients and Methods In this retrospective study we analysed the data of all pregnant women with a positive cfDNA result seen between 09/2013 and 12/2019. Women were either referred due to the positive result or the test was initiated in our practice. The primary parameter of interest was the concordance of cfDNA tests with confirmatory genetic testing. Results We encountered 81 cases with a positive cfDNA test (T21: 49.4%; T18: 9.9%; T13: 8.6%; SCA: 22.2%; 22q12del: 8.6%). The PPV was 95.0% for T21, but considerably lower for T18 (55.6%) and T13 (28.6%). For SCAs it was 23.1% and no case with DiGeorge syndrome was confirmed. 63% of the patients had not received a fetal anomaly scan before cfDNA testing. In first-trimester fetuses with a cfDNA test predicting an autosomal aneuploidy, fetal anomalies were detected in 90.3% of the cases. No false positive case had an abnormal US result. Conclusions Despite the excellent specificity of cfDNA tests, the PPV for aneuploidies other than T21 is low in routine practice. In discordance with the current guidelines, cfDNA test is often used without a previous detailed anomaly scan. Our data provide valuable information to assist patient counselling and shared decision making.

Two Rare Variants of Down Syndrome: Down-Turner Syndrome and Down Syndrome with Translocation (13;14): A Case Report

In the present paper, we report two rare cases of Down syndrome (DS); mosaic Down-Turner syndrome and DS with rob (13;14). Patient 1 karyotype is mos 45,X[41] / 47, XX,+21[59] and patient 2 karyotype is 46, XY, rob (13;14)(q10;q10),+21. With these two unusual cases, we aimed to look at the most common numerical and structural chromosome anomalies from a different window and evaluate the phenotypic effect in the presence of different chromosomal anomalies. Our main goal is to evaluate the phenotypic characteristics of these two rare variants in the light of literature.

Prevalence of chromosome anomalies in a deer farm with fertility decline in Malaysia

Background: A number of factors are known to reduce fertility rate in animals and one of the important categories of such factors is chromosome anomalies. They can occur with or without causing phenotypic abnormalities on animals; in some cases, they may directly affect meiosis, gametogenesis and the viability of conceptus. In many instances, balanced structural rearrangements can be transmitted to offspring, affecting fertility in subsequent generations. Aim: This work investigated the occurrence of chromosome aberrations in Rusa timorensis, Rusa unicolor and Axis axis raised in a nucleus deer farm in Malaysia with a history of declining fertility of unknown origin. Materials & methods: Blood samples were collected from 60 animals through venipuncture, cultured for 72 h and arrested at metaphase. SmartType® and Ideokar® software were used to karyotype the chromosomes. Results: We found 15 out of the 60 animals screened from both sexes harbor some form of chromosome aberration. Chromosomal aberrations exist at the rate of 25% and may not be unconnected with the observed reduced fertility on the farm. Further investigations should be carried out, especially on the offspring of the studied animals to transmission of these aberrations. The animals that are confirmed to transmit the chromosomal aberrations should be culled to arrest the propagation of their abnormalities.

Microarray expression studies on bone marrow of patients with Shwachman-Diamond syndrome in relation to deletion of the long arm of chromosome 20, other chromosome anomalies or normal karyotype

Background Clonal chromosome changes are often found in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS). The most frequent ones include an isochromosome of the long arm of chromosome 7, i (7)(q10), and an interstitial deletion of the long arm of chromosome 20, del (20)(q). These two imbalances are mechanisms of somatic genetic rescue. The literature offers few expression studies on SDS. Results We report the expression analysis of bone marrow (BM) cells of patients with SDS in relation to normal karyotype or to the presence of clonal chromosome anomalies: del (20)(q) (five cases), i (7)(q10) (one case), and other anomalies (two cases). The study was performed using the microarray technique considering the whole transcriptome (WT) and three gene subsets selected as relevant in BM functions. The expression patterns of nine healthy controls and SDS patients with or without chromosome anomalies in the bone marrow showed clear differences. Conclusions There is a significant difference between gene expression in the BM of SDS patients and healthy subjects, both at the WT level and in the selected gene sets. The deletion del (20)(q), with the EIF6 gene consistently lost, even in patients with the smallest losses of material, changes the transcription pattern: a low proportion of abnormal cells led to a pattern similar to SDS patients without acquired anomalies, whereas a high proportion yields a pattern similar to healthy subjects. Hence, the benign prognostic value of del (20)(q). The case of i (7)(q10) showed a transcription pattern similar to healthy subjects, paralleling the positive prognostic role of this anomaly as well.

Karyotype Evaluation in Patients with Premature Ovarian Failure

INTRODUCTION: Chromosome anomalies are one of the major causes of premature ovarian failure and the importance of chromosome analysis in reproductive management has been confirmed. Numerical and structural chromosome anomalies, especially structural anomalies of the X chromosome, X-autosome translocations and X-chromosome aneuploidies, are the chromosome anomalies most commonly described in the literature. In this study, we aimed to evaluate the frequency and type of chromosomal anomalies in the patients with premature ovarian failure admitted to our clinic and to discuss the findings in the light of current literature and to provide guidance to new studies. METHODS: The files of the patients, who were diagnosed with premature ovarian failure between 2002 and 2017, were screened from the archive of the division of reproductive endocrinology and infertility in the department of obstetrics and gynecology at our center. 65 patients were included in the study. Information about age, smoking, alcohol use, age at menarche and menapose, hormone replacement therapy usage, additional disease and obstetric history were obtained from files. The laboratory results of the patients were obtained from files. FSH, LH, estradiol, prolactin, TSH, fT3, fT4, Anti-TPO, Anti-TG, TRAB, cortisol, ANA, Insulin, fasting blood glucose, LDL, HDL, triglyceride, total cholesterol, anti-Mullerian hormone levels were recorded from files. The karyotype results were recorded from files. RESULTS: The mean age at diagnosis was 32.6 years.The mean body mass index was 23.4(kg/m²). 60(92.3%) had normal karyotype(46+XX). 5(7.7%) had abnormal karyotype(4 had 46+XX/45+X and 1 had 46+XY/45+X). The mean value of fT3 is significantly higher in cases with normal karyotype(p: 0.019). DISCUSSION AND CONCLUSION: Considering the high rate of X chromosome loss in patients with premature ovarian failure, we can say that premature ovarian failure manifests itself in a wide spectrum. In conclusion, it can be said that cytogenetic studies should be evaluated routinely in cases with premature ovarian failure regardless of age.

The case of prenatal ultrasound diagnosis of isolate bilateral anophthalmia

The case of prenatal ultrasound diagnosis of isolate bilateral anophthalmia at 19–20 weeks of gestation is presented. The pregnancy was terminated, the diagnosis was confirmed. The incidence of this rare fetus pathology at Sverdlovsk region during last 10 years and combination with other defect and chromosome anomalies is analyzed. Possibility of early detection of eyes pathology and necessity of genetic consulting of patients with burdened familial history are discussed.