The genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) are heterogeneous and highly ethnic-specific. We describe GJB2 (connexin 26) variants and carrier frequencies as part of our study and summarize previously reported ones for the Romanian population. In total, 284 unrelated children with bilateral congenital NSHL were enrolled between 2009 and 2018 in northwestern Romania. A tiered diagnostic approach was used: all subjects were tested for c.35delG, c.71G>A and deletions in GJB6 (connexin 30) using PCR-based methods. Furthermore, 124 cases undiagnosed at this stage were analyzed by multiplex-ligation-dependent probe amplifications (MLPA), probe mix P163, and sequencing of GJB2 exon 2. Targeted allele-specific PCR/restriction fragment length polymorphism (RFLP) established definite ethio-pathogenical diagnosis for 72/284 (25.35%) of the cohort. Out of the 124 further analyzed, in 12 cases (9.67%), we found compound heterozygous point mutations in GJB2. We identified one case of deletion of exon 1 of the WFS1 (wolframin) gene. Carrier status evaluation used Illumina Infinium Global Screening Array (GSA) genotyping: the HINT cohort-416 individuals in northwest Romania, and the FUSE cohort-472 individuals in southwest Romania. GSA variants yielded a cumulated risk allele presence of 0.0284. A tiered diagnostic approach may be efficient in diagnosing ARNSHL. The summarized contributions to Romanian descriptive epidemiology of ARNSHL shows that pathogenic variants in the GJB2 gene are frequent among NSHL cases and have high carrier rates, especially for c.35delG and c.71G>A. These findings may serve in health strategy development.

Background: Conditions associated with BRCA1/2 pathogenic (PVs) or likely pathogenic variants (LPVs) are often severe. The early detection of carrier status is ideal, as it provides options for effective case management. Materials and Methods: The study involved 58 patients with a personal and familial history of breast cancer (BC) who underwent genetic testing at the Regional Centre for Medical Genetics Dolj over a three-year period. An immunohistochemical panel (HER2, ER, PR, and Ki-67) was used to define the molecular subtypes of breast tumors. The AmpliSeq for Illumina BRCA Panel was used to evaluate germline variants in the BRCA1 and BRCA2 genes in patients with BC. The χ² test and Fisher’s exact test were used to compare the different parameters studied. Results: Our findings revealed that 15.5% of the patients carried either BRCA1 or BRCA2 PVs or LPVs. BRCA1 carriers had aggressive tumors whereas BRCA2 carriers had rather low-grade tumors. Conclusions: The study revealed that PVs in both BRCA genes have a significant frequency among BC patients in our region, and BRCA1 carriers tend to develop more aggressive tumors than carriers of BRCA2 PVs and patients with no germline PVs in either of the two genes. These observations could provide new epidemiologic data for this disease in our region and contribute further to the development of national screening strategies.

The impact of genetic variability on embryogenesis and fetus development established medical genetics as essential for the prevention of congenital anomalies, early detection and appropriate management. Advances in ultrasonography equipment and technique allow early detection of many congenital malformations. In addition, genetic testing can be performed in a prenatal setting on a variety of biological samples obtained by invasive and noninvasive procedures: chorionic villus sampling, amniocentesis, cordocentesis, or maternal blood collection (i.e., cell free fetal DNA). In the past, only a small percentage of congenital anomalies had a readily identifiable etiology; genetic diagnostic procedures can provide at least some of the answers for the remaining unsolved cases. Undoubtedly, the need for appropriate case management and counseling justifies the importance of uncovering the underlying genetic cause of birth defects. In this chapter, we will focus on genetic counseling in congenital anomalies, including isolated congenital anomalies and preimplantation genetic diagnosis. Genetic counseling provides information and support, assisting parents in making informed decisions. Through this process, parents learn about the risk of having a newborn with a congenital malformation and the nature of the disorder and its natural history, are advised on available testing for that particular case, and discuss options for risk management and family planning.

Background and Objectives: Recurrent pregnancy loss (RPL) is a multifactorial condition, encompassing genetic, anatomical, immunological, endocrine, as well as infectious and environmental factors; however, the etiology remains elusive in a substantial number of cases. Genetic factors linked to RPL include parental karyotype abnormalities (e.g., translocations, inversions, copy number variants), an increase in sperm aneuploidy, fetal microchimerism, severe skewing of X chromosome inactivation, and various gene polymorphisms. Our study aims to explore the value of routine conventional parental karyotyping in couples with RPL. Materials and Methods: A total of 213 couples (426 individuals) with a history of RPL were enrolled in this retrospective study. The peripheral blood samples included in this study were referred to the Human Genomics Laboratory of the University of Medicine and Pharmacy in Craiova, Romania, for conventional cytogenetic analysis between January 2013 and December 2023, by the Outpatient Medical Genetics Clinic of the Emergency Clinical County Hospital of Craiova. Chromosome analysis was performed using standard protocols and karyotypes were reported according to ISCN. Results: Out of 426 patients provided with conventional G-banded chromosome analysis, 410 had a normal karyotype (96.2%) and 16 had chromosome abnormalities (3.8%). The most common chromosomal abnormalities were reciprocal and Robertsonian translocations, with chromosomes 8, 11, 14, and 21 being most frequently involved. A single numerical anomaly was detected (47,XYY). One or multiple chromosomal polymorphisms were identified in 104 subjects (24.4%). In addition, we conducted a stratified analysis of the unselected group and detected chromosome abnormalities in only four cases (0.94%). Conclusions: Our results are consistent with recommendations for paternal karyotyping after an individual risk assessment in instances such as a previous live birth with congenital anomalies and/or the detection of unbalanced chromosomes or a translocation in product of conception or chorionic villi/amniotic fluid samples. In the absence of a positive history, blindly karyotyping couples may prove too expensive and labor intensive, while providing no information on fertility status or live birth rates.

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality, influenced by both genetic and epigenetic factors. Long non-coding RNAs (lncRNAs) such as GAS5 and CASC8 have been implicated in cancer susceptibility. This study aimed to assess the association of GAS5 rs145204276 ins/del and CASC8 rs10505477 A>G polymorphisms with CRC risk in a Romanian population. A case-control study was conducted, including 156 CRC patients and 195 healthy controls. Genotyping for GAS5 and CASC8 polymorphisms was performed using real-time PCR, and the association with CRC risk was evaluated using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The carriers of GAS5 rs145204276 del allele was significantly associated with increased CRC risk (OR: 2.13, 95% CI: 1.24–3.63, p = 0.005) in a dominant model. In the subgroup analysis, the association of GAS5 rs145204276 ins/del polymorphism was restricted to distal colon cancer cases (OR: 2.98, 95% CI: 1.57–5.66, p = 0.001), advanced tumor stages (III + IV) (OR: 2.54, 95% CI: 1.31–4.91, p = 0.007), and poorly differentiated tumors (G3) (OR: 3.98, 95% CI: 1.49–10.59, p = 0.009). No significant correlation was found for the CASC8 rs10505477 A>G polymorphism. GAS5 rs145204276 polymorphism may influence CRC susceptibility, particularly in distal tumors and advanced stages. However, CASC8 rs10505477 polymorphism showed no association with CRC risk in this Romanian cohort.

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility.