Identification of Lynch syndrome risk variants in the Romanian population.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadTwo familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high-risk CRC mutations in the Romanian population. We performed whole-genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559-1G>C).European Union EE

CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, karyotype analysis by G-banding was performed from peripheral blood in 967 women infertility. Results: Chromosomal abnormalities were found to 79 women (8,17%). The percentage of chromosomal abnormalities in the studied population correlates with the data in the literature. Chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions

Cell free fetal DNA testing in maternal blood of Romanian pregnant women

Background: The discovery of circulating fetal DNA in maternal blood led to the discovery of new strategies to perform noninvasive testing for prenatal diagnosis. Objective: The purpose of the study was to detect fetal aneuploidy at chromosomes 13, 18, 21, X, and Y by analysis of fetal cell-free DNA from maternal blood, without endangering pregnancy. Materials and Methods: This retrospective study has been performed in Bucharest at Medlife Maternal and Fetal Medicine Department between 2013-2014. In total 201 women were offered noninvasive prenatal test. Maternal plasma samples were collected from women at greater than 9 weeks of gestation after informed consent and genetics counseling. Results: From 201 patients; 28 (13.93%) had screening test with high risk for trisomy 21, 116 (57.71%) had advanced maternal age, 1 (0.49%) had second trimester ultrasound markers and the remaining 56 patients (27.86%) performed the test on request. Of those patients, 189 (94.02%) had a “low risk” result (99% risk) all for trisomy 21 (T21). T21 was confirmed by amniocentesis in 1 patient and the other 4 patients declined confirmation. The 7 remaining patients (3.48%) had a low fetal fraction of DNA. Conclusion: It is probably that prenatal diagnosis using fetal DNA in maternal blood would play an increasingly role in the future practice of prenatal testing because of high accuracy

Large duodenal nonepithelial tumor – diagnostic and treatment difficulties

Spitalul Clinic de Urgență, București, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Se prezintă un caz clinic particular de tumora voluminoasă cadran abdominal superior drept, oligosimptomatică evidențiată imagistic incidental în contextul explorărilor pentru suspiciunea confirmată de litiaza veziculară, la pacienta relativ tanară (41 ani) fără antecedente semnificative. Explorarea ecografică nu poate preciza apartenența topografică a formațiunii (hipoecogena, net conturată 4/5 cm).Tomografia sugereaăa apartenența pancreatică la nivelul procesului uncinat, structura neomogenă (solid-chistica) și dimensiuni 7/11 cm. Explorarea intraoperatorie permite stabilirea originii tumorii la nivelul D III, la dreapta pediculului mezenteric superior. Optiunea terapeutică a constat în disecția tumorii fără sacrificii tisulare semnificative și rezecția bazei de implantare la nivelul D III cu endoGIA (cartus alb). Examenul histopatologic atesăa originea non-epitelială a tumorii. Evoluție postoperatorie simplă.We present a particular case of a large right upper quadrant mass, incidentaly found on imaging studies used for confirming gallstone disease, in a relatively young patient (41 of age) with minimal presenting features and no past medical or surgical history. The US scan cannot point out the origin of the mass ( 4/5 cm, hypoechoic, circumscribed margins). The CT scan suggests it arises from the uncinate process of the pancreas (7/11 cm, inhomogeneous, solid-cystic architecture). Intraoperative findings show third part of the duodenum as the originating tissue, right of the superior mesenteric artery . The therapeutic option is tumor resection with minimal duodenal tissue sacrifice, using endoGIA stappler. Histological examination attests nonepithelial origin of the tumor. Uncomplicated postoperative evolution

ISOLATED DENTINOGENESIS IMPERFECTA AND IN ASSOCIATION WITH OSTEOGENESIS IMPERFECTA – A LITERATURE REVIEW

Dental development is part of the craniofacial organogenesis, starting from the pluripotent cephalic neural crest cells, continuing with their movement towards the first pharyngeal arch and leading to the development of many elements of the craniofacial structures.Tooth developmental disorders can be caused by genetic abnormalities at any level of the genomic information (chromosomal, monogenic, polygenic-multifactorial). Dentin genetic abnormalities have been known for several years and include two entities: dentinogenesis imperfecta (DI) and dentin dysplasia (DD). Osteogenesis imperfecta (OI) (also known as brittle bone disease) is a connective tissue disorder (collagen disorders) characterized by bone fragility leading to recurrent bone fractures and in the severe forms to bone deformities and shortening. 12 clearly described types of OI and 2 other OI phenotypical entities have been described until present, the best known being due to various COL1A1 and COL1A2 mutations, (genes which encode for the collagen type I pro-alpha 1 and 2 polypeptide chains). Although DI is part of the clinical features reported in OI, not all types of OI have dentin genetic anomalies.For patients with OI, it is extremely important that the clinician understands the possible dental implications associated with the disease. Children with OI should be examined as soon as teeth are erupted to prevent loss of tooth structure and seen frequently to restore any new enamel fracture and maintain their oral health. Genetic testing is available in single-gene or multigene panel analysis and is essential in the diagnosis and in defining the type of OI or DI of each patient

Prenatal Diagnosis and Outcome of Tracheal Agenesis as Part of Congenital High Airway Obstruction Syndrome. Case Presentation and Literature Review

Tracheal atresia is an extremely rare condition whereby a partial or total obstruction of the trachea is seen. It is almost always lethal, with just a handful of cases that ended with a good outcome. In this study we report on a 15-week male fetus, diagnosed with hyperechogenic lungs, midline heart position and inverted diaphragm. Sonographic findings suggest congenital High Airway Obstruction Syndrome (CHAOS) An ultrasound scan and fetal MRI were not able to point out the exact obstruction level. In spite of extensive counselling, the parents opted to carry on with the pregnancy. Fetal demise was noted on a scan at 19 weeks gestation. After the elective termination of pregnancy, a post-mortem examination showed partial tracheal atresia with no other anomalies. Despite technological progress in CHAOS syndrome, a precise diagnosis and accurate prognosis remain elusive

Prenatal Diagnosis and Outcome of Tracheal Agenesis as Part of Congenital High Airway Obstruction Syndrome. Case Presentation and Literature Review

Tracheal atresia is an extremely rare condition whereby a partial or total obstruction of the trachea is seen. It is almost always lethal, with just a handful of cases that ended with a good outcome. In this study we report on a 15-week male fetus, diagnosed with hyperechogenic lungs, midline heart position and inverted diaphragm. Sonographic findings suggest congenital High Airway Obstruction Syndrome (CHAOS) An ultrasound scan and fetal MRI were not able to point out the exact obstruction level. In spite of extensive counselling, the parents opted to carry on with the pregnancy. Fetal demise was noted on a scan at 19 weeks gestation. After the elective termination of pregnancy, a post-mortem examination showed partial tracheal atresia with no other anomalies. Despite technological progress in CHAOS syndrome, a precise diagnosis and accurate prognosis remain elusive

HUMAN HEREDITARY ENAMELABNORMALITIES – MOLECULAR FACTORS AND GENETIC COUNSELLING

Defective enamel formation may result either from factors of environmental origin or from genetic abnormality. Such genetically determined enamel malformations have been described in patients with chromosomal anomalies and with inherited single gene defects. Enamel is a principal component of the dentition, and defects in this hard tissue are associated with a wide variety of diseases. Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair. Amelogenesis imperfecta (AI) is a group of genetically and phenotypically diverse forms of defective tooth enamel development. Progress has been made regarding the definition of the genetic basis of AI, but the exact mechanism for the biomineralization process remains largely unknown. The list of genes associated with enamel defects has grown tremendously over the past decade. The molecular pathways involved in the development of enamel defects are diverse, and the functionality of the genes and gene products is heterogeneous. Syndrome-associated enamel defects are caused by many genes that affect other tissues, including eye, kidney, brain, and skin. As with enamel defects, early diagnosis and preventive care are essential for successful management of dentine defects. Patients who have a family history of dentine defects such as dentinogenesis imperfecta or those with medical conditions known to be associated with dentine defects such as hypophosphataemia and osteogenesis imperfecta should be screened early for dental problems

Fatal Association of Mirror and Eisenmenger Syndrome during the COVID-19 Pandemic

Mirror syndrome (MS) or Ballantyne’s syndrome is a rare maternal condition that can be life-threatening for both mother and fetus. The condition is characterized by maternal signs and symptoms similar to those seen in preeclampsia in the setting of fetal hydrops. Despite recent advances in the field of maternal-fetal medicine, the etiopathogenesis of MS remains elusive. For patients and doctors, the COVID-19 pandemic has become an extra hurdle to overcome. The following case illustrates how patients’ non-compliance associated with mirror syndrome and SARS-CoV-2 infection led to the tragic end of a 19-year-old patient. Therefore, knowledge of the signs and symptoms of mirror syndrome should always be part of the armamentarium of every obstetrician

Hyperglycosylated-hCG: Its Role in Trophoblast Invasion and Intrauterine Growth Restriction

Human chorionic gonadotropin (hCG) is produced by the placenta and its roles have been studied for over a century, being the first known pregnancy-related protein. Although its main role is to stimulate the production of progesterone by corpus luteal cells, hCG does not represent just one biologically active molecule, but a group of at least five variants, produced by different cells and each with different functions. The hyperglycosylated variant of hCG (H-hCG) plays a key role in trophoblast invasion, placental development and fetal growth. During trophoblast invasion, H-hCG promotes extravillous cytotrophoblast cells to infiltrate the decidua, and also to colonize and remodel the spiral arteries in to low resistance, larger-diameter vessels. As fetal growth is heavily reliant on nutrient availability, impaired trophoblast invasion and remodeling of the uterine arteries, leads to a defective perfusion of the placenta and fetal growth restriction. Understanding the function of H-hCG in the evolution of the placenta might unveil new ways to manage and treat fetal growth restriction