The effect of progesterone supplementation in women with threatened miscarriage on fetal fraction in non-invasive prenatal testing: A matched case-control study.

AIM: To evaluate the effect of progesterone use on fetal fraction (FF) in non-invasive prenatal testing (NIPT) due to the threat of first trimester miscarriage. METHODS: This case control study included the pregnant who were referred to our clinic for non-invasive prenatal testing. The patients were categorized into three groups: Pregnant women with vaginal bleeding and using progesterone, pregnant women with vaginal bleeding and not using progesterone, and pregnant women without bleeding. The groups were formed by matching gestational week. Women with multiple pregnancy, BMI (body mass index) ≥25, abnormal fetal karyotype, and chronic disease were excluded from the study. Maternal characteristics, FF of the NIPT were recruited from the computer based medical records. RESULTS: A total of 10,275 NIPT tests were performed during the study period. 3% of the patients (n = 308) were found at risk of miscarriage. 100 patients with a vaginal bleeding and 50 control patients were matched. The median value of the fetal fraction ratio was found to be 6.55 in pregnant women without vaginal bleeding, 7.05 in pregnant women who had vaginal bleeding and using progesterone, and 7.3 in pregnant women who had vaginal bleeding and did not use progesterone. Although the fetal fraction ratio was found to be higher in pregnant women with vaginal bleeding and lower in progesterone users, this situation could not reach the level of statistical significance (p = 0.351). CONCLUSIONS: The fetal fraction rate in maternal blood is not affected in pregnant women who use progesterone due to vaginal bleeding in early gestational weeks.

Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome.

OBJECTIVE: Joubert syndrome is a neurodevelopmental disorder with a distinctive hindbrain malformation called molar tooth sign, causing motor and cognitive impairments. More than 40 genes have been associated with Joubert syndrome. We aim to describe a group of Joubert syndrome patients clinically and genetically emphasizing organ involvement. METHODS: We retrospectively collected clinical information and molecular diagnosis data of 22 patients with Joubert syndrome from multiple facilities. Clinical exome or whole-exome sequencing were performed to identify causal variations in genes. RESULTS: The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma. Portal hypertension and esophageal varices as liver and polycystic kidney disease and nephronophthisis as kidney involvement was encountered in our patients. The HYLS1 gene, which commonly causes hydrolethalus syndrome 1, was also associated with Joubert syndrome in one of our patients. A mild phenotype with hypophyseal hormone deficiencies without the classical molar tooth sign was observed with compound heterozygous and likely pathogenic variants not reported before in the KATNIP gene. CONCLUSION: Some rare variants that display prominent genetic heterogeneity with variable severity are first reported in our patients. In our study of 22 Joubert syndrome patients, CPLANE1 is the most affected gene, and Joubert syndrome as a ciliopathy is possible without a classical molar tooth sign, like in the KATNIP gene-affected patients.

Does Follicle-Stimulating Hormone Receptor Polymorphism Status Affect In vitro Fertilization-Intracytoplasmic Sperm Injection Results and Live Birth Rate? A Retrospective Study.

Background: Follicle-stimulating hormone (FSH) plays a key role in fertility and shows its effect through the FSH receptor (FSHR), which is localized in cells. Aims: The aim of this study was to examine pregnancy outcomes and responses to controlled ovarian stimulation according to FSHR polymorphism types. Study Setting and Design: The study was retrospective, and included patients who applied to the University of Health Sciences Tepecik Training and Research Hospital in vitro fertilization (IVF) Unit during 2018 and 2019. Materials and Methods: Patients who underwent IVF-intracytoplasmic sperm injection and at the same time studied FSHR gene polymorphism in the genetic unit of our hospital were included in the study. Statistical Analysis: The Kruskal-Wallis test was used for multiple comparisons of continuous variables. The Chi-square test was used for categorical variables between groups. Results: A total of 143 patients who met our criteria were included in the study. 14% (n = 20) of the patients are also homozygous natural (Asn/Asn) type; 44.7% (n = 64) of the heterozygous mutant (Asn/Ser) type; 41.3% (n = 59) of them were homozygous mutant (Ser/Ser) type. There was no statistically significant difference between the groups in terms of pregnancy rate per started cycle, ongoing pregnancy per started cycle, ongoing pregnancy per embryo transfer and live birth per embryo transfer. A significant difference was observed between peak E2 and peak progesterone levels between Asn/Ser and Ser/Ser groups, and the levels of these hormones were lower in the Ser/Ser group (P = 0.018 and P = 0.016, respectively). Ovarian responses were classified as poor (≤3 oocytes), normal (4-20 oocytes) and hyperresponse (≥20 oocytes) according to the oocyte count. Accordingly, the number of patients with poor response was higher in the Ser/Ser group (P = 0.011). Conclusions: Ser/Ser polymorphism is characterised by a poor ovarian response. Despite this, polymorphisms in the FSHR gene do not seem to affect the results of pregnancy per started cycle, ongoing pregnancy per started cycle, ongoing pregnancy per embryo transfer and live birth per embryo transfer.

Can the Cell-free DNA Test Predict Placenta Accreta Spectrum or Placenta Previa Totalis?

BACKGROUND: Following the discovery that fetal DNA originates from the trophoblastic cells of the placenta, the contribution of the cell-free DNA test in placenta-related obstetric complications has begun to be investigated. Compared to uncomplicated pregnancies, higher fetal fractions were detected in placenta accreta spectrum and placenta previa, which are among placenta-related obstetric complications. However, this data applies only to advanced gestational weeks. AIM: To investigate the possible predictive value of fetal fraction in cell-free DNA tests in pregnancies with placenta previa and placenta accreta spectrum in early gestational ages. MATERIALS AND METHODS: This study was conducted in women who were screened via cell-free DNA tests for common aneuploidies in the first and second trimester and subsequently diagnosed with placenta previa or placenta accreta spectrum. After the diagnosis was confirmed with a C-section, fetal fractions were retrospectively compared to a control group with a history of an uncomplicated C-section who were also previously screened by cell-free DNA test. RESULTS: The median and interquartile range (IQR) of fetal fractions for placenta previa (n=19), placenta accreta spectrum (n=7), and control groups (n=85) were 8.1 (6-10), 6.8 (6.7-10.7), and 7.1 (4.7-9.65), respectively. No statistically significant difference was observed among the three groups in terms of fetal fractions (p=0.587). CONCLUSIONS: According to our data, we did not observe any relationship between placental invasion abnormalities vs. control group or placenta previa vs. control group using the fetal fractions of the cell-free DNA test. Furthermore, we could not confirm a predictive role and/or any additional clinical contribution. We believe that future studies focusing on placental mRNA might be more helpful than cell-free fetal DNA testing.

The relation between distant metastasis and genetic change type in stage IV lung adenocarcinoma patients at diagnosis.

INTRODUCTION: Brain metastasis prevalence is higher in patients with positive epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) and C-ROS oncogene 1 (ROS-1) fusion change in lung adenocarcinoma. OBJECTIVES: The purpose of our study is to investigate the relation between the genetic change type and the initial distant metastasis in stage IV lung adenocarcinoma patients with genetic changes. METHODS: The study was conducted between January 2007 and December 2018 in a retrospective fashion with patients who had lung cancer diagnosed as stage IV adenocarcinoma. The relation between genetic mutation change (EGFR, ALK or ROS-1) and distant metastasis was analysed. RESULTS: A total of 845 patients were included in the study. The median age was 62 (28-88). It was determined that lung and pleura metastases were more frequent at a significant level in patients with positive EGFR mutation (P = 0.032, P = 0.004, respectively). In patients with positive ALK fusion change, pleura metastasis was determined to be more frequent (P = 0.001). Multiple metastases were determined to be significantly more in patients with positive ALK fusion change than single metastasis (P = 0.02). CONCLUSION: In patients with EGFR mutant lung adenocarcinoma, lung and pleura metastasis is more frequent and pleura metastasis is more frequent in ALK positive adenocarcinoma. Additionally, multiple organ metastases are higher in ALK positive lung adenocarcinoma.

Evaluation of chromosomal abnormalities and Y-chromosome microdeletions in 1696 Turkish cases with primary male infertility: A single-center study.

OBJECTIVE: The aim of this study was to determine the frequencies of chromosomal abnormalities and Y-chromosome microdeletions in Turkish cases with primary male infertility in a single center. MATERIAL AND METHODS: Chromosomal abnormalities and Y-chromosome microdeletions were investigated in 1696 cases with primary male infertility between 2012 and 2017. Karyotype analyzes and Y-chromosome microdeletions analyzes [azoospermia factor (AZF) regions] were performed in all cases by using standard cytogenetic methods and the multiplex polymerase chain reaction method, respectively. RESULTS: Chromosomal abnormalities were found in 142 cases (8.4%; 142/1696). Y-chromosome microdeletions were detected in 46 cases (2.7%; 46/1696). Y-chromosome microdeletions in the AZFc region were found in 20 of 46 cases (43%). CONCLUSION: This study is one of the few were a large number of cases was studied in Turkey. It indicates that cytogenetic and Y-chromosome microdeletion studies should be conducted in cases with primary male infertility prior to selecting assisted reproductive techniques.

First-Line Molecular Genetic Evaluation of Autosomal Recessive Non-Syndromic Hearing Loss.

OBJECTIVE: The aim of this study is to investigate the efficiency of a first-line molecular genetic evaluation approach, in children with deafness. METHODS: Patients who were found to have sensorineural hearing loss by age-appropriate audiological tests were selected for the molecular genetic evaluation. The molecular genetic evaluation was carried out with GJB2 gene sequence analysis and mtDNA m.1555A>G mutation Restriction Fragment Length Polymorphism (RFLP) analysis. Additionally, in a small group of patients, hearing loss Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was done out to identify the possible role of copy number changes. RESULTS: In this Turkish cohort, which included 104 index patients and 78 relatives, 33 (31.7%) had Pathogenic/Likely Pathogenic variants. One or more GJB2 sequence variants were identified in 46 (44.1%) of the 104 index patients. The homozygous c.35delG mutation by itself explained the etiology in 24% of our ARSNHL group. In one (5%) of the 20 patients of MLPA group, a hemizygous deletion in POU3F4 gene was detected. CONCLUSION: In our Turkish cohort, we applied a first-line molecular genetic evaluation approach using GJB2 gene sequence analysis and mtDNA m.1555A>G RFLP analysis. This approach revealed the genetic etiology of 44.1% of our index patients. Additionaly, the results of hearing loss MLPA analysis revealed the limited role of copy number changes in this patient group. Furthermore, with a detailed genotype-phenotype association workup, 2 rare cases of Deafness with Palmoplantar Hyperkeratosis and Keratitis-Ichthyosis-Deafness syndrome were reported.

The clinical and molecular features of three Turkish patients with a rare genetic disorder: 2q37 deletion syndrome.

Gürsoy S, Kutbay YB, Özdemir TR, Hazan F. The clinical and molecular features of three Turkish patients with a rare genetic disorder: 2q37 deletion syndrome. Turk J Pediatr 2019; 61: 589-593. Chromosome 2q37 deletion syndrome is a rare chromosomal disorder which is characterized by mild-moderate intellectual disability, brachymetaphalangy of digits 3-5, short stature, obesity, hypotonia and characteristic facial appearance. Here, we report three Turkish patients who have 2q37 deletion in aCGH analysis with various sizes (9.08 Mb, 2.3 Mb and 2.021 Mb, respectively). HDAC4 gene, which is a class II histone deacetylase, has been considered to be associated with most of the features including brachymetaphalangy and intellectual disability. The deletion region included HDAC4 gene in the two patients. However, all of the patients had intellectual disability, especially with a cheerful mood. Some autistic features were detected in one of our patients. Although two patients had some skeletal findings, the deletion region did not contain HDAC4 gene in one of the patients. We suggest that our findings support understanding and updating knowledge on the phenotype-genotype correlation in patients with 2q37 deletion syndrome.

QF-PCR in invasive prenatal diagnosis: a single-center experience in Turkey.

BACKGROUND/AIM: QF-PCR has been used for more than 20 years. It is based on investigation of polymorphic short tandem repeats (STRs) and is widely used for prenatal rapid aneuploidy detection. MATERIALS AND METHODS: We report retrospectively our prenatal diagnosis results between January 2012 and May 2014 in Tepecik Training and Research Hospital Genetic Diagnostic Center. Prenatal diagnosis was recommended in 6800 high-risk pregnancies and 2883 patients agreed to invasive diagnosis. Chromosome analysis and QF-PCR were performed in all patients. RESULTS: Normal results were reported in 2711 cases by fetal karyotyping and in 2706 cases by QF-PCR. Anomaly detection rates were similar for the two methods (5.09% for karyotyping and 4.02% for QF-PCR). CONCLUSION: QF-PCR is a fast and reliable prenatal diagnosis method in all indication groups and may be preferred as the sole prenatal investigation in patients without fetal ultrasonographic findings.