Family History Of Congenital Disease Research Articles

Abstract PO4-08-02: Genetic testing among patients with triple-negative breast cancer at a single health system: a quality improvement project

Abstract Background: Breast cancer is the most common type and the second leading cause of cancer-related deaths in women. Approximately 15-20% of patients have triple-negative breast cancer (TNBC) at diagnosis. TNBC is aggressive, difficult to treat, prone to relapse, and associated with an increased mortality rate. The incidence of BRCA1/2 mutation is about 20% in patients with TNBC (Hartman et al. 2012). Despite the high prevalence of germline mutations in cancer susceptibility genes among TNBC patients, many do not received genetic counseling (GC) or genetic testing (GT). National Comprehensive Cancer Network (NCCN) guidelines now recommend GT for all patients with TNBC, regardless of age, especially after the approval of Poly Adenosine diphosphate Ribose Polymerase (PARP) inhibitors for targeted therapy against BRCA1/2 mutations. The aim of this quality improvement (QI) project was to identify patients with TNBC who did not receive GT and design an intervention to understand potential barriers to receiving GC and GT. Methods: We implemented a QI project to identify previously diagnosed adult patients with TNBC (18 years and older) of any stage (early or advanced/metastatic) without prior GT or family history of genetic disorders with active follow-up at the Henry Ford health breast cancer clinic. Eligible patients diagnosed between January 2015 and January 2020 from the Syapse Learning Health Network database were included. Baseline information as well as additional data including demographics, breast cancer treatment details, and whether GT and/or GC was offered or not was obtained through electronic health record review after institutional review board committee approval. Bi-monthly meetings were held amongst breast cancer providers, genetic counselors, and nurse navigators to develop an intervention to contact the patients who did not undergo GT and/or GC. After obtaining the list of patients who did not undergo GT and/or GC despite meeting eligibility criteria, they were contacted by their primary breast cancer providers via telephone regarding their willingness to obtain GT and/or GC at this time and participate in a questionnaire-based interview to understand barriers towards the same. Results: In the 5 years, a total of 123 patients were noted to have been diagnosed with triple-negative breast cancer. Of these, 93 patients were actively being followed at the Henry Ford breast clinic at the time of the QI project. 2 of the 9 patients who underwent GT and GC were positive for BRCA1/2 mutation. Of the remaining 83 patients that did not receive GC or GT, 65 (78.3%) had no clear reason explained in the chart, 27 patients (32.5%) chose not to get tested, 23 (27.7%) were not deemed to be eligible upon initial assessment and 4 (4.8%) had pending orders placed by breast surgeons upon initial diagnosis. Unfortunately, 29 of these 83 patients were noted to have been deceased when the intervention was being designed. Remaining 54 patients were contacted by their primary breast cancer oncologists to determine their willingness in participating in the questionnaire-based interview. Conclusion: Based on the results of our QI project, we have now developed a process to contact the identified patients and renew the offer for GT and GC as well as participation in a questionnaire-based interview to understand the potential barriers to testing. We also plan to improve physician education and awareness by conducting mini sessions during our annual symposium meetings as well as grand rounds and develop a protocol for ordering GT and GC in patients with TNBC at our institution. Citation Format: Manasi Godbole, Mary Nyhuis, Travis Washburn, Joann Hirth, Haythem Ali. Genetic testing among patients with triple-negative breast cancer at a single health system: a quality improvement project [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-02.

Support for Research Biobanks Among Medical Students in the Republic of Kazakhstan.

Background: Over the past few years, several biobanks have been organized in the Republic of Kazakhstan (RoK). As research biobanks are becoming an increasingly important tool for precision medicine, they require competent biobankers who will help disseminate the idea of biobanking throughout the society and support donation for research purposes. This study aimed to assess the support for research biobanks among medical students (MSs) in Kazakhstan. Methods: This research includes data from an anonymous, self-administered online questionnaire regarding MSs' support for research biobanks in the RoK. Results: Only 212 (31.3%) MSs have heard of biobanks and 466 (68.7%) have not. Students who were biobank-aware held more positive views regarding biobanks, were more likely to support the idea of establishing a research biobank in Kazakhstan, and expressed a greater willingness to donate their biological material for research purposes. Students' awareness of biobanks was also associated with the respondents' motivations to donate. Students who were familiar with biobanks tended to be motivated by altruistic reasons more often, and those unfamiliar with biobanks tended to indicate selfish motives. Students' attitudes toward donation to various types of research and biobanks were influenced by their awareness of biobanks, any family history of genetic disease, experience of chronic disease, declared religiousness, hospitalization history, blood donor status, and year of study. Conclusion: Since MSs' awareness of research biobanks is low, there is an urgent need for biobank education in Kazakhstan.

Assessment of genetic familiarity and genetic knowledge among Palestinian university students

Background and aimsGenetic knowledge and familiarity among the population represent the lane toward effective participation in social decisions regarding genetic issues. This cross sectional research aimed to assess genetic knowledge and familiarity among university students in Palestine.MethodsThe familiarity with genetics was evaluated using the Genetic Literacy and Comprehension instrument (GLAC), and genetic knowledge was measured using a 16-item scale of prevalent genetic concepts.ResultsAmong the 624 participants, 59.5% were females. 38.8% reported family history of genetic diseases. The genetic familiarity mean score was 4.83 and the genetic knowledge mean total score was 11.5. Students’ genetic familiarity was high for the terms chromosome and genetic while it was low for the terms sporadic and vulnerability. Genetic knowledge was highest for gene definition while it was the lowest regarding the number of human genes. The age group, year of study, and learning genetic courses were the significant predictors of familiarity among medical students. The year of study, family history of genetic diseases, parental consanguinity, and learning genetic courses were the significant variables associated with genetic knowledge among medical students. Regarding the non-medical group of participants, all study variables were significant for both familiarity and knowledge scores except for age group with familiarity.ConclusionGenetic familiarity and knowledge among Palestinian university students are inadequate. Consanguinity and hereditary disorders are prevalent in Palestine. These findings encourage university stakeholders to take action to improve genetic knowledge and familiarity among students through both appropriate pedagogical and non-pedagogical interventions.

Preimplantation Genetic Testing (PGT) for Non-Lethal Correctable Conditions Through Population Carrier Screening

An increasing number of patients without family history of genetic disease are referred for preimplantation genetic testing of monogenic disorders (PGT-M) after ascertainment through population (expanded) carrier screening (ECS), increasing the proportion of non-lethal correctable genetic conditions in PGT-M indication profile. The aim of this paper is to analyze the current dynamics of these changes in our PGT-M series, which is the world’s largest PGT-M experience. This was analyzed using our PGT-M for two prevalent examples of non-lethal correctable genetic conditions, phenylketonuria (PKU) and hereditary hearing loss (HHL) during the period of 2005-2022. During this period, 91 PGT-M cycles were performed for PKU, involving testing for 108 mutant alleles in PAH gene, and 262 PGT-M cycles for HHL, involving testing for up to 300 mutations in 13 different genes causing hearing loss. PGT-M for these non-lethal correctable conditions resulted in the birth of 54 babies free of PKU and 134 children free of HHL. Dynamics of PGT-M referrals during this period of 17 years demonstrated the shift from retrospective to prospective application of PGT-M for both conditions, with 87% of prospective PGT-M performed for PKU, and 82% for HHL, performed for couples who had no affected relatives with PKU or HHL. These at-risk couples were ascertained through ECS in the last decade, making it possible to provide the option of prospective PGT-M for these non-lethal correctable conditions.

Genetic diseases and associated risk factors in some Libyan districts: A cross sectional study

Genetic disorders are caused by defects in the genetic material ranging from point mutations to chromosomal deletions. Manifesting of recessive defects requires the mutation inheritance from both parents, whereas dominant disorders require the mutation inheritance from one parent. This study aimed to investigate the rate of genetic disorders among Libyan participants with genetic disorders, to investigate their most causative risk factors and the level of awareness of these diseases. This cross sectional study was carried out through a questionnaire with a set of questions about genetic diseases distributed both on paper and electronically. 256 participants have generic disorders from different regions of Libya were involved. The participant's answers were collected from July 2021 to February 2022. The findings showed that the most prevalent genetic diseases were blood disorders 13.7%, CI=13.3-15.4), Down syndrome (13.3%, CI=9.5-17.4), autoimmune diseases (12.1%, CI=8.2-16.0), hereditary cancer (9.0%, CI=5.1-12.9) and congenital malformations (7.4%, CI= 4.1-10.9). The results showed that consanguineous marriage was a risk factor associated with the incidence of genetic diseases (P= 0.000, CI= 3.34-3.48) and there was a high rate of second-degree consanguineous marriage for the parents of participant patients (55.0%, n=141). Moreover, there was a family history of genetic disease (53.5%). The findings showed a lack of awareness of genetic diseases and their nature among the participants’ families. Data from this survey should be taken into account by the health authorities to outline a policy to prevent these genetic disorders in the country

Public knowledge of and attitudes toward genetics and genetic testing in Brunei Darussalam.

The world has been experiencing encouraging research in genetics, but current public knowledge, awareness, and perception of this area remain unknown for Brunei Darussalam. This study aimed to investigate the Brunei population's genetics and genetic testing literacy, and their attitude toward them. A cross-sectional study was carried out targeting public population in Brunei Darussalam. Questionnaires on knowledge and attitudes were randomly distributed in frequented venues in the Brunei-Muara district and uploaded online for distribution through social media. Responses were scored and analyzed using appropriate statistical methods. Overall, the sample population (n = 474) comprised 75.7% female, 64.3% aged 18-29 years old, 39.7% with a bachelor's degree, and 2.3% and 5.3% with a personal history and family history of genetic disease(s), respectively. Younger participants scored higher for disease-related questions and showed more concern on the impact of testing on employment but were more fearful of testing. Higher educational qualifications were associated with a higher knowledge score, a more optimistic view on DNA research, and less reluctance to take a genetic test for an untreatable disease. Participants with a personal history of genetic disease(s) were more knowledgeable and displayed higher curiosity. Participants with a family history of genetic disease(s) were also more knowledgeable and would want testing even for an untreatable disease. Significantly less was known about the social consequences of testing compared to the medical possibilities. Investigating the knowledge and attitudes of the population is vital preceding efforts toward national adaptation of genetic testing, keeping in mind the various obstacles and issues surrounding the subject.

How do members of the public expect to use variants of uncertain significance in their health care? A population-based survey

PurposeGenomic sequencing can generate complex results, including variants of uncertain significance (VUS). In general, VUS should not inform clinical decision-making. This study aimed to assess the public's expected management of VUS. MethodsAn online, hypothetical survey was conducted among members of the Canadian public preceded by an educational video. Participants were randomized to 1 of 2 arms, VUS or pathogenic variant in a colorectal cancer gene, and asked which types of health services they expected to use for this result. Expected health service use was compared between randomization arms, and associations between participants’ sociodemographic characteristics, attitudes, and medical history were explored. ResultsAmong 1003 respondents (completion rate 60%), more participants expected to use each type of health service for a pathogenic variant than for a VUS. However, a considerable proportion of participants expected to request monitoring (73.4%) and consult health care providers (60.9%) for a VUS. There was evidence to support associations between expectation to use health services for a VUS with family history of genetic disease, family history of cancer, education, and attitudes toward health care and technology. ConclusionMany participants expected to use health services for a VUS in a colorectal cancer predisposition gene, suggesting a potential disconnect between patients’ expectations for VUS management and guideline-recommended care.

Current attitudes toward carrier screening for spinal muscular atrophy among pregnant women in Eastern China.

Spinal muscular atrophy (SMA) is an autosomal recessive and often fatal neurological disease. However, very little is known about the attitudes toward SMA carrier screening among Chinese pregnant people. In this study, pregnant women in Eastern China who were undergoing routine chromosomal screening programs were invited to view an educational video about SMA and complete a 26-item survey regarding their attitudes toward SMA screening by scanning a specific quick response code. A total of 1673 questionnaires were collected, and 81.1% of respondents were willing to undergo self-funded screening. If the screening program were included in the medical insurance, 97.8% of respondents were willing to accept screening. The important reasons for supporting SMA screening were a belief that it could help them make better reproductive decisions and avoid having a child with SMA. The key reason for declining SMA screening was not having a family history of genetic diseases. A higher score for SMA genetics knowledge was associated with a greater willingness to undergo SMA screening. We concluded that pregnant women in Eastern China had positive attitudes toward SMA carrier screening. Improving genetic knowledge and including the screening program in medical insurance would support the widespread implementation of SMA carrier screening. Steps should be taken to offer SMA carrier screening along with pre- and posttest education and genetic counseling to raise awareness and reduce misconceptions regarding SMA.

Considerations on the use of carrier screening testing in human reproduction: comparison between recommendations from the Italian Society of Human Genetics and other international societies

Carrier screening (CS) is a term used to describe a genetic test performed on individuals without family history of genetic disorders, to investigate the carrier status for pathogenic variants associated with multiple recessive conditions. The advent of next-generation sequencing enabled simultaneous CS for an increasing number of conditions; however, a consensus on which diseases to include in gene panels and how to best develop the provision of CS is far to be reached. Therefore, the provision of CS is jeopardized and inconsistent and requires solving several important issues. In 2020, the Italian Society of Human Genetics (SIGU) established a working group composed of clinical and laboratory geneticists from public and private fields to elaborate a document to define indications and best practice of CS provision for couples planning a pregnancy. Hereby, we present the outcome of the Italian working group's activity and compare it with previously published international recommendations (American College of Medical Genetics and Genomics (ACMG), American College of Obstetricians and Gynecologists (ACOG), and Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG)). We determine a core message on genetic counseling and nine main subject categories to explore, spanning from goals and execution to technical scientific, ethical, and socio-economic topics. Moreover, a level of agreement on the most critical points is discussed using a 5-point agreement scale, demonstrating a high level of consensus among the four societies. This document is intended to provide genetic and healthcare professionals involved in human reproduction with guidance regarding the clinical implementation of CS.

Participant Choice towards Receiving Potential Additional Findings in an Australian Nephrology Research Genomics Study.

: BackgroundThe choices of participants in nephrology research genomics studies about receiving additional findings (AFs) are unclear as are participant factors that might influence those choices. Methods: Participant choices and factors potentially impacting decisions about AFs were examined in an Australian study applying research genomic testing following uninformative diagnostic genetic testing for suspected monogenic kidney disease. Results: 93% of participants (195/210) chose to receive potential AFs. There were no statistically significant differences between those consenting to receive AFs or not in terms of gender (p = 0.97), median age (p = 0.56), being personally affected by the inherited kidney disease of interest (p = 0.38), or by the inheritance pattern (p = 0.12–0.19). Participants were more likely to choose not to receive AFs if the family proband presented in adulthood (p = 0.01), if there was family history of another genetic disorder (p = 0.01), and where the consent process was undertaken by an adult nephrologist (p = 0.01). Conclusion: The majority of participants in this nephrology research genomics study chose to receive potential AFs. Younger age of the family proband, family history of an alternate genetic disorder, and consenting by some multidisciplinary team members might impact upon participant choices.

S3723 A Rare Cause of Upper Gastrointestinal Bleeding: Gastric Synovial Sarcoma

Introduction: Synovial sarcoma is an uncommon type of malignant mesenchymal neoplasm commonly found within joints of the extremities and very rarely found in the GI tract. Genetic sequencing techniques used as an adjunct to histochemical markers have proven indispensable for diagnosis following biopsy. We present a rare subtype of soft tissue neoplasm called primary gastric synovial sarcoma as cause for gastrointestinal bleeding in a middle-aged Hispanic patient. Case Description/Methods: A 51-year-old male with a medical history of Hypertension, and Diabetes was brought to the ER due to a syncopal episode. Patient denied abdominal pain, weight loss, hematemesis, hematochezia, hematuria, or melena. Physical exam was remarkable only for pale conjunctiva. Laboratory results remarkable for a hemoglobin of 5 g/dL warranting multiple packed red blood cell transfusions. Colonoscopy was performed with normal findings. Following upper GI endoscopy, a mid gastric body 3 cm polypoid irregular mass with shallow ulcerations was found. The patient was referred for endoscopic ultrasound revealing a 25 by 21 mm heterogenous hypoechoic mass in the greater curvature confined to mucosal layer. The acquired specimen displayed characteristics of a high-grade tumor with multiple negative markers (table 1). Therefore, an SS18 FISH test (18q11.2 probe) was performed and the results show the presence of translocation t(X,18) (p11.2;q11.2), consistent with a poorly differentiated synovial sarcoma, a spindle cell monophasic subtype. Completeness of resection of the tumor could not be documented so the patient was referred to surgery for partial gastrectomy of the involved area. The remaining tumor measured 0.7 cm, invaded the submucosal layer but all margins and lymph nodes were uninvolved. A subsequent PET/CT scan did not reveal evidence or residual or metastatic disease. (Figure) Discussion: This is the first known case of a primary gastric synovial sarcoma, in a patient of Puerto Rican ethnicity, without family history of genetic disorders, radiation exposure or previous malignancy. Prognosis remains challenging due to the small number of reported cases with surgical resection as the mainstay of treatment. Therefore, it is crucial to continue to identify and diagnose this rare malignancy to better inform treatment and prognostic decisions going forward.Figure 1.: Figure A: Friable lobular mass at greater curvature of stomach. Figure B: Endoscopic ultrasound revealed 2.5 by 2.1 cm heterogeneous hyperechoic mass at greater curvature of stomach confined to mucosal layer. Figure C: Picture of specimen following endoscopic mucosal resection. Table 1. - histochemical stains / Fluorescence in situ Hybridization performed for identification of tumor Tumor Marker Result Lymphoma CD20, CD23 Negative Gastrointestinal stromal tumor CD117, CD34, DOG-1 Negative Angiosarcoma CD34 Negative Leiomyosarcoma caldesmon, MSA, SMA, Desmin Negative Sarcomatoid carcinoma AE1, AE3 Negative Spindle cell melanoma S100, SMB 45 Negative Synovial Sarcoma SS18 FISH test (18q11.2) t(X;18)(p11.2;q11.2)

THE INDIRECT INFLUENCE OF BASKETBALL ON CARDIAC AND CEREBRAL VASCULARIZATION

ABSTRACT Introduction: Some experimental research has proved that long-term basketball exercises can effectively improve physical fitness, promote growth and improve motor functions. However, studies exploring the specific effects of this sport on cardiac and cerebral vascularization are still scarce. Objective: We aimed to study, through experimental analysis, if the activities derived from basketball sport can have some influence on cardiac and cerebral vascularization. Methods: Twelve students with no family history of genetic diseases and in good health, who regularly practice amateur basketball, were followed for 8 weeks. Weight, height, body mass index, body fat rate, maximum oxygen consumption, hemoglobin, and indicators of lipid metabolism were analyzed. Results: After long-term basketball exercises, the body fat rate of these college students decreased significantly, and total serum cholesterol and low-density lipoprotein also show significant differences compared with the control group. Conclusion: Through the processing and analysis of the experimental data, it can be concluded that basketball can effectively reduce the human body fat rate, maintain a healthy body shape, and indirectly reduce the risk of cardiovascular and cerebrovascular diseases. Level of evidence II; Therapeutic studies - investigation of treatment results.

THE PREVALENCE AND RISK FACTORS FOR HYPERBILIRUBINEMIA IN NEONATES

Background: Jaundice is very common in the neonatal period of life especially hyperbilirubinemia>12 mg/dl. Although it is not a major cause of mortality, it is an important cause of morbidity. So, assessment of the prevalence and risk factors of neonatal jaundice is very important. Objectives: The objectives of the study were to estimate the prevalence,to identify the risk factors and to findout the association between hyperbilirubinemia with selected neonatal,maternal,environmental and socio demographic variablesand to identify the risk factors. Methodology: This descriptive cross sectional survey study was conducted among 200 neonates of 37 completed weeks of gestation. Subjects were selected by using total enumerative sampling.Transcutaneous bilirubin was measured by bilirubinometer,clinical and demographic variables collected by using semi structured questionnaire and the risk factors were assessed by interview schedule. Results:Research showed that most of neonates (81.5%) had Transcutaneous bilirubin level more than 12mg/dl, out of that (15% )subjects had elevated level of bilirubin 15- 20mg/dl. It is concluded that there is high prevalence of hyperbilirubinemia among neonates . It is evident that neonates developed hyperbilirubinemia by 48 to 72 hours. It is inferred that prevalence of hyperbilirubinemia was high at 72 hours (56.5%) after birth compared to 48 hours of birth (38%). There was a significant association between level of hyperbilirubinemia and family history of genetic diseases (P=0.003),parity (p=0.03, χ2=4.37),mode of conception(p=0.012, χ2=6.37), and gestational age(P=0.04),gender of the neonate (p=0.004, χ2=8.1)and duration of second stage of labour (p=0.026, χ2=7.27). The study revealed that the family history of genetic diseases (p=0.004),(OR=0.09) at level of significance 0.05,is a risk factor leads to hyperbilirubinemia. Conclusion: Neonatal jaundice is a leading cause of hospitalisation in the first few weeks of life throughout the world.Though major complications may arise like kernicterus,encephalopathy and neural sequlae.Hence there is an exigent need for assessing the bilirubin value in the routine neonatal assessment.

Large mandibular mass in a newborn

A newborn boy in the neonatal intensive care unit was referred shortly after birth for evaluation of a large mandibular mass. The boy was born at 39-week, 1-day gestational age to a healthy 30-year-old, gravida 2 para 1 mother. Pregnancy and delivery were uncomplicated. Maternal prenatal laboratory tests and fetal ultrasonography at 20-weeks’ gestation were normal. There was no family history of genetic diseases or similar lesions. The boy was born at 3,003 grams with good Apgar scores. Physical examination revealed a pink mass protruding out of the oral cavity (Figure 1).

Pregnant women's experiences of non-invasive prenatal testing (NIPT) in Japan: A qualitative study.

In Japan, prenatal testing does not include a publicly insured routine health check-up for pregnant women. Hence, taking advantage of such prenatal testing procedures is still not an option for a majority of Japanese women. However, social support systems for children and adults with disabilities have been developed with the assumption that people with disabilities will continue receiving support from their family members, especially their mothers. In this study, we described pregnant women's experiences regarding noninvasive prenatal testing (NIPT) within the context of their physical experiences during the NIPT process, Japanese society, and their medical circumstances. Women with no family history of genetic diseases or fetal disabilities and who had also received negative results after the NIPT explanation were recruited. Altogether, 15 women participated in the biographical narrative interview. The data were subjected to reflexive thematic analysis and signified advanced age for pregnancy as a trigger for both the women's consideration regarding receiving NIPT and interventions from their families and social group members. Participants considered themselves as the main caretaker for the older adults and individuals with disabilities and thus were afraid of the multiple responsibilities inherent in this reality. They were also concerned about the impact on any other siblings if the baby had disabilities. In addition, participants encounter physical and mental changes during the timeframe of the NIPT processes. Hence, as their fetuses mature, the psychological bonds the women develop with them are constantly evolving, and participants with histories of miscarriages or possible miscarriages expressed concerned not only about the results of NIPT but also about the specific possibility of losing their child in any way. In conclusion, the continuous support of these women throughout the NIPT process and social efforts for the improvement of the welfare system for people with disabilities are required to utilize NIPT effectively.

Diagnosis of 22q11.2 Deletion Syndrome in a Child With Congenital Heart Disease and Facial Dimorphism: A Case Report

22q11.2 deletion syndrome is caused by a deletion in chromosome 22q11.2 and has more than 180 distinct phenotypes; however, no finding is pathognomonic or even mandatory. This syndrome can be diagnosed by fluorescence in situ hybridization. Thus, we report herein a patient from Manaus, Brazil, who has congenital heart disease and facial dimorphism with the presence of 22q11.2 deletion in the N25 region. Male patient, a 1-year-old son of non-consanguineous parents and without a family history of genetic disease. The patient was hospitalized in the cardiac intensive care unit of the Francisca Mendes University Hospital for surgery. The patient was diagnosed with interventricular communication, low atrial implantation, hypertelorism, and macroglossia. The FISH result revealed the presence of a proximal deletion in the N25 region (22q11.2) in only one of the pairs in chromosome 22. This finding revealed a diagnosis of 22q11.2 deletion syndrome, in other words, a hemizygotes deletion with haploinsufficiency of the CLTCL1 gene in this region. However, it is valid to say that the CLTCL1 gene is related to the clinical picture of the patient reported in this study. Cytogenetic analysis was essential for the etiological diagnosis and revealed 22q11.2 deletion in the N25 region, which resulted in 22q11.2 deletion syndrome. The importance of diagnosing this syndrome lies in the best therapeutic conduct, thus allowing a better quality of life for the patient and adequate genetic counseling. Other cytogenetic studies are essential in order to elucidate the size of the deletion and low copy repeats involved in this deletion.

Chromosomal microarray analysis in fetuses with high-risk prenatal indications: A retrospective study in China

ObjectiveThe present study aimed to determine the diagnostic value of prenatal chromosomal microarray analysis (CMA) for fetuses with several indications of being at high risk for various conditions. Materials and methodsThis retrospective analysis included 1256 pregnancies that were prenatally evaluated due to high-risk indications using invasive CMA. The indications for invasive prenatal diagnosis mainly included ultrasound anomalies, high-risk for maternal serum screening (MSS), high-risk for non-invasive prenatal tests (NIPT), family history of genetic disorders or birth defects, and advanced maternal age (AMA). The rate of clinically significant genomic imbalances between the different groups was compared. ResultsThe overall prenatal diagnostic yield was 98 (7.8%) of 1256 pregnancies. Clinically significant genomic aberrations were identified in 2 (1.5%) of 132 patients with non-structural ultrasound anomalies, 36 (12.7%) of 283 with structural ultrasound anomalies, 2 (4.5%) of 44 at high-risk for MSS, 38 (26.6%) of 143 at high-risk for NIPT, 11 (3.8%) of 288 with a family history, and 7 (2.1%) of 328 with AMA. Submicroscopic findings were identified in 29 fetuses, 19 of whom showed structural ultrasound anomalies. ConclusionThe diagnostic yields of CMA for pregnancies with different indications greatly varied. CMA could serve as a first-tier test for structural anomalies, especially multiple anomalies, craniofacial dysplasia, urinary defects, and cardiac dysplasia. Our results have important implications for genetic counseling.

Willingness to participate in genome testing: a survey of public attitudes from Qatar

Genomics has the potential to revolutionize medical approaches to disease prevention, diagnosis, and treatment, but it does not come without challenges. The success of a national population-based genome program, like the Qatar Genome Program (QGP), depends on the willingness of citizens to donate samples and take up genomic testing services. This study explores public attitudes of the Qatari population toward genetic testing and toward participating in the QGP. A representative sample of 837 adult Qataris was surveyed in May 2016. Approximately 71% of respondents surveyed reported that they were willing to participate in the activities of the QGP. Willingness to participate was significantly associated with basic literacy in genetics, a family history of genetic diseases, and previous experience with genetic testing through premarital screening. Respondents cited the desire to know more about their health status as the principle motivation for participating, while lack of time and information were reported as the most important barriers. With QGP plans to ramp up the scale of its national operation toward more integration into clinical care settings, it is critical to understand public attitudes and their determinants. The results demonstrate public support but also identify the need for more education and individual counseling that not only provide information on the process, challenges, and benefits of genomic testing, but that also address concerns about information security.

Family history risk assessment by a genetic counselor is a critical step in screening all patients in the ART clinic.

The family history is the cornerstone of the genetic risk assessment. Taking a detailed family history helps ensure that important genetic information is not overlooked and that any appropriate testing and/or information is provided to the patient prior to pregnancy. Guidelines from the American Society for Reproductive Medicine (ASRM) suggest a review of personal and family history of genetic disease and prior genetic test results that may affect the course of treatment, with patients being counseled about additional genetic testing that may be indicated before starting treatment relating to their personal or family history. When issues arise as a result of this evaluation, referral to a genetics specialist is recommended. As the following cases demonstrate, implementation of a routine genetic counseling screening program for all patients using assisted reproductive technology (ART) provides immense benefits so that important indications for referral to a genetic counselor are not missed.

Genetic diagnosis in the fetus.

Many genetic disorders are detectable in the prenatal period, and the capacity to identify them has increased remarkably as molecular genetic testing techniques continue to improve and become incorporated into clinical practice. The indications for prenatal genetic testing vary widely, including follow-up of an anomaly found by routine ultrasound or maternal aneuploidy screening, a family history of genetic disease, advanced maternal or paternal age, or evaluation of a low-risk pregnancy due to parental concern. The interpretation of genetic variants identified in the prenatal period poses unique challenges due to the lack of ability for deep phenotyping as well as the option to make critical decisions regarding pregnancy continuation and perinatal management. In this review, we address the various modalities currently available and commonly used for genetic testing, including preimplantation genetic testing of embryos, cell-free DNA testing, and diagnostic procedures such as chorionic villous sampling, amniocentesis, or percutaneous umbilical blood sampling, from which samples may be sent for a wide variety of genetic tests. We discuss the difference between these modalities for the genetic diagnosis of a fetus, their strengths and weaknesses, and strategies for their optimal use in order to direct perinatal care.