Genetic Consultation Research Articles

Abstract B005: Impact of molecular profiling and ESCAT classification on patient outcome: The experience of Institut Curie Molecular Tumor Board

Abstract Introduction: The European Society of Medical Oncology Scale of Actionability of molecular Targets (ESCAT) classification system provides a standardized framework for categorizing genomic alterations (GA) of advanced cancer patients. We aimed to analyze the impact of matched therapies administered based on GAs identified through Institut Curie Molecular Tumor Board (MTB) between January 2018 and December 2022, according to ESCAT classification. Patients and methods: Between 2018 and 2022, 1,445 patients were discussed at Institut Curie MTB. Inclusion criteria were pre-defined as: adult patients (>18 years) with advanced or rare cancers. Tumors characteristics, pathological and genomic analyses, MTB conclusions, and follow-up after MTB were collected. Molecular analyses included a custom in-house NGS panel of 571 genes (DRAGON) and targeted RNAseq (ARCHER FusionPlex® CTL panel) or WGS, WES and RNAseq performed on the SEQOIA platform as part of the French Genomic Medecine Plan 2025. Clinical endpoints were Objective Response Rates (ORR), Progression-Free Survival (PFS) and Overall Survival (OS). ORR, PFS and OS of the population of patients receiving matched therapies were analyzed according to ESCAT Tiers. Results: Median patients age was 59 in the global MTB population (range=18-95; n=1,445) and mostly females (968/1,445; 67%). Most frequent tumors were from breast (20%), head and neck (10%), pancreas (10%), colon/rectum (9%), ovary (7%), lung (7%), soft tissue (7%), uterus (6%) or uveal melanoma (5%). Of the 1,445 patients, 995 had a tumor molecular profiling (69%). Actionable GAs were found in 576/995 (58%) of patients and 211/995 (21%) patients were oriented towards matched therapy. Simultaneously, some patients have also been referred to a genetic consultation when GA may correspond to a known predisposition gene. Among the 211 patients oriented towards matched therapy and after clinical evaluation for each patient, 101/211 (47%) representing 101/995 (10%) of the total patients actually received a matched therapy according to 102 actionable GAs identified through MTB analysis. The main actionable GAs detected were found in PIK3CA (12%), ERBB2 (11%), BRCA2 (6%) and FGFR3 (5%) genes. Among these, 40/102 GAs (40%) were classified as tier I, 4 (4%) as tier II, 35 (35%) as tier III, 18 (18%) as tier IV and 5 (5%) as tier X according to ESCAT. For those patients, PFS and OS were significantly improved when treatment was administered based on ESCAT tiers I/II (p=0.0486 for PFS, and p=0.0224 for OS). Worst clinical outcomes were observed for hypothetical targets classified as Tiers III and IV. Conclusions: High throughput screening was feasible for a majority of patients enrolled in the MTB. Among the patients screened, actionable GAs are identified in 58% of the patients. Yet 21% were oriented to matched therapy. Finally, 10% of patients were eventually treated with matched therapy, with a favorable outcome observed in patients with ESCAT Tiers I/II. Citation Format: Maud Kamal, Kimya Rahmani Narj Abadi, Raphaël Sanchez, Célia Dupain, Isabelle Guillou, Grégoire Marret, Zahra Castel Ajgal, Marie Paule Sablin, Cindy Neuzillet, Amani Asnacios Lecerf, Edith Borcoman, Ségolène Hescot, Florence Coussy, Manuel Rodrigues, Nicolas Girard, Sarah Watson, Julien Masliah Planchon, Jennifer Wong, Abderaouf Hamza, Celine Callens, Olfa Trabelsi Grati, Samia Melaabi, Keltouma Driouch, Emmanuelle Mouret-Fourme, Chrystelle Colas, Samantha Antonio, Odette Mariani, Michèle Nijnikoff, Anne Vincent-Salomon, Yves Allory, Ivan Bieche, Christophe Le Tourneau. Impact of molecular profiling and ESCAT classification on patient outcome: The experience of Institut Curie Molecular Tumor Board [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B005.

Telemedicine Versus Traditional In-Person Consultations: Comparison of Patient Satisfaction Rates.

Introduction: Data on patient satisfaction with the provision of genetic consultations using telemedicine are limited, especially those involving children. We compared patient satisfaction rates with telemedicine services versus traditional in-person encounters. Methods: A cross-sectional questionnaire-based study was conducted between January and June 2020. Questionnaires were distributed online to 1,672 consecutive patients who had received genetic counseling at our Genetics Institute in the clinical fields of adult and pediatric genetics, oncogenetics, and prenatal genetics, through in-person and/or telemedicine consultation. We used Likert scale with scores of 4-5 representing "satisfied"-"very satisfied" and 1-2 representing "very unsatisfied"-"unsatisfied." Results: The response rate was 27.3% (400 adults and 57 children <18 years), including 330 who had received in-person consultations (72.2%), 80 telemedicine consultations (17.5%), and 47 both consultations (10.3%). Mean satisfactory scores of 4-5 were reported by 82.1% in the in-person group versus 82.5% in the telemedicine group (p = 0.88). Mean scores of 1-2 were reported by 6.3% in the in-person group versus 11.2% in the telemedicine group (p = 0.31). No pediatric telemedicine group patient (n 12 = ) gave scores of 1-2 compared with 2/33 (6%) patients who had in-person pediatric consultations (p = 0.62). Most responders who had been counseled through telemedicine (n = 127, 84%) indicated willingness to use genetic services through telemedicine again. Conclusions: Users of genetic counseling through telemedicine, especially in the pediatric age group, were very satisfied at rates comparable to those of in-person consultations. Future research should evaluate patient compliance and views according to session type, information provided (e.g., diagnostic vs. negative results), and its nature (good vs. bad news).

Attention should be paid to the importance of genetic testing in clinical practice of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS) is a progressive and fatal neurodegenerative disease that mainly involves upper and lower motor neurons. It lacks clear biomarkers and can be clearly diagnosed only one and a half years after the onset. Gene test is of great significance for diagnosis, prognosis and genetic counseling. In recent years, several gene therapy studies have entered the clinical trial stage of ALS, among which the antisense oligonucleotide therapy targeting the pathogenic variation of the superoxide dismutase 1 (SOD1) gene has been launched, and it is urgent to carry out routine gene test in clinical practice. On the basis of progress of ALS gene research in recent years, family history, age of onset and typical clinical manifestations of patients are no longer considered as the basis for genetic testing. However, the target genes of clinical gene testing needs to be further clarified according to the diagnostic purpose, the testing method and scheme need to be standardized, and the genetic consultation before testing should be paid attention to, and the informed consent should be fully achieved.

Primary Ovarian Insufficiency: Current Understanding and Diagnostic Approaches

Primary ovarian insufficiency (POI) is a medical condition where ovarian function stops prematurely, typically before the age of 40. This condition leads to infertility and produces symptoms similar to those experienced during menopause. Although the origins of POIs are diverse, genetic elements substantially influence their emergence. This assessment delves into the genetic facets of POI, covering genetic triggers, detection, and genetic consultation. We scrutinize the genes linked to POI and their function in ovarian activity, as well as the genetic deviations and mutations that foster POI onset. We also examine the challenges and limitations of genetic testing and counseling for POI and suggest ways to address these challenges. This review offers a thorough examination of the existing understanding of the genetic factors linked to Primary Ovarian Insufficiency (POI) emphasizing the critical need for further investigation in this field.

АНАЛІЗ ДИНАМІКИ НАРОДЖЕННЯ ДІТЕЙ З АУТОСОМНИМИ ТРИСОМІЯМИ ПО ХМЕЛЬНИЦЬКІЙ ОБЛАСТІ

In the face of challenging modern demographic conditions, the imperative of preserving human life is becoming increasingly urgent. Environmental pollution, a deteriorating ecological landscape, imbalanced nutrition, unhealthy lifestyles, the accumulation of hereditary defects, and a rising genetic burden collectively exert adverse effects on Ukraine's gene pool. This unfortunate scenario contributes to the increased rate of early child mortality and the birth of children with disabilities [7].&#x0D; The objective of this study was to analyze the trends in child births with Down, Edwards, and Patau syndromes while investigating the influence of maternal age on the incidence of these genetic anomalies in the Khmelnytskyi region from 2017 to 2021.&#x0D; We conducted an analysis of statistical data pertaining to newborns, utilizing information from the Main Statistical Office in the Khmelnytskyi region. This investigation was undertaken in collaboration with the medical and genetic consultation department of the KP "Khmelnytskyi City Perinatal Center." It involved a comprehensive review of outpatient records for patients born with Down, Edwards, and Patau syndromes, aimed at understanding the clinical condition of the infants and the course of pregnancy in their mothers.&#x0D; The analysis revealed that a total of 50,475 babies were born in the region over the course of five years. However, an annual decrease in the birth rate was observed, with an average reduction of 705 children per year. The incidence rate of newborns with Down syndrome, Edwards syndrome, and Patau syndrome ranged from 0.10% to 0.13%. During the research period, 45 children with Down syndrome were born in the Khmelnytskyi region. Cytogenetic analysis indicated that 39 of these children (87 %) had a complete trisomy, 4 had a mosaic form (9 %), and 2 (4 %) had a translocation form. Children with complete trisomy exhibited four or more phenotypic features simultaneously. In the region, 12 children were born with Edwards syndrome, including 9 with complete trisomy and 3 with a mosaic form. No newborns were identified with partial trisomy. Cases included both full-term and premature births, as well as instances of infant mortality. Two children with Patau syndrome were born (1 boy in 2017 and 1 girl in 2019), both with complete trisomy. They were born full-term but with low birth weight and multiple developmental disabilities, with one child surviving for 12 hours and the other for 31 hours.&#x0D; Upon analyzing the age of the parents of the probands, it was discovered that the majority (38 mothers, 64 %) were not within the age risk group for having a child with trisomy. This suggests that women of any age can be at risk of having a child with trisomy. Thus, there is a clear need for medical-genetic counseling and prenatal screening for every pregnant woman during the first trimester of pregnancy.

Genetic Investigations in Turkish Idiopathic Pancreatitis Patients Show Unique Characteristics.

Pancreatitis is one of the leading causes of digestive system-related hospital admissions, and it has a genetic background in a considerable portion of the patients. In this study, we aimed to investigate the genetic risk factors of idiopathic pancreatitis in Turkish patients and the contribution of copy number variations to the pathogenesis. Idiopathic pancreatitis is defined as failure to detect risk factors despite comprehensive clinical assessments. Next-generation sequencing and multiple ligand-dependent probe amplification of PRSS1, SPINK1, CTRC, and CFTR were performed. For further genotype-phenotype correlations, patients were also questioned for the age of onset, family history, and pancreatic divisum. A total of 68 idiopathic pancreatitis cases were enrolled. Variants with potential clinical significance of PRSS1 were identified in 13.4%, SPINK1 in 6.3%, CTRC in 4.7%, and CFTR in 26.5% of the patients. No copy number variants were seen in any of these genes. At least 7.4% of the participants had complex genetic etiology involving 2 genes. At least 42.6% of the participants had a potential genetic risk factor. Five novel genetic variants were identified, and distinctive genetic risk factors of Turkish population were shown. The results showed that genetic etiology was frequent in pancreatitis and it was even more prominent in patients with early-onset disease. Considering that genetic risk factors may be informative for decisionmaking in the treatment options in addition to providing extensive prognostic value and familial genetic consultation; clinicians need to be more eager to offer genetic tests to pancreatitis patients.

Congenital neuroblastoma presenting as profound neonatal metabolic acidosis with systemic hypertension: Case report.

Clinical collapse in the newborn most often occurs secondary to sepsis, delivery complications, congenital cardiac defects, or inborn errors of metabolism. We report on a neonate with respiratory, cardiac, and hepatic failure, with disproportionate metabolic acidosis and systemic hypertension, found to be caused by a congenital neuroblastoma. A term infant presented to our Level IV NICU via emergent transport at 12 hours of life with clinical and laboratory findings consistent with respiratory, cardiac, and hepatic failure. Typical workup for sepsis and cardiac etiology was unrevealing. The infant was noted to have systemic hypertension despite prolonged capillary refill. A profound metabolic acidosis led the primary team to pursue a genetics consult. In the course of the workup for disorders of metabolism, a urine organic acids panel revealed an elevated HVA (homovanillic acid) and VMA (vanillylmandelic acid), the metabolites of the neurotransmitters epinephrine, norepinephrine and dopamine. Subsequent abdominal ultrasound and chest/abdomen CT revealed a large heterogeneous mass with internal vascular flow and scattered calcifications arising from the medial limb of the left adrenal gland, consistent with neuroblastoma. Although rare, neuroblastomas can present clinically in the perinatal period in a manner requiring immediate life-saving intervention. Providers should consider the diagnosis in the setting of a newborn with a sepsis-like syndrome or profound metabolic acidosis presenting along with systemic hypertension without clear underlying etiology.

Genetics of infertility: a paradigm shift for medically assisted reproduction.

The field of reproductive genetics has undergone significant advancements with the completion of the Human Genome Project and the development of high-throughput sequencing techniques. This has led to the identification of numerous genes involved in both male and female infertility, revolutionizing the diagnosis and management of infertility patients. Genetic investigations, including karyotyping, specific genetic tests, and high-throughput sequencing, have become essential in determining the genetic causes of infertility. Moreover, the integration of genetics into reproductive medicine has expanded the scope of care to include not only affected individuals or couples but also their family members. Genetic consultations and counselling play a crucial role in identifying potentially affected relatives and offering tailored therapy and the possibility of fertility preservation. Despite the current limited therapeutic options, an increasing understanding of genotype-phenotype correlations in infertility genes holds promise for improved treatment outcomes. The availability of genetic diagnostic tools has reduced the number of idiopathic infertility cases by providing accurate aetiological diagnoses. The transition from research to clinical practice in reproductive genetics requires the establishment of genetic consultations and data warehousing systems to provide up-to-date information on gene-disease relationships. Overall, the integration of genetics into reproductive medicine has brought about a paradigm shift, emphasizing the familial dimension of infertility and offering new possibilities for personalized care and family planning.

Incidental finding at methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA): how to proceed?

Introduction: Since the advent of new generation sequencing, professionals are aware of the possibility of obtaining findings unrelated to the pathology under study. However, this possibility is usually forgotten in the case of studies aimed at a single gene or region. We report a case of a 16-month-old girl with clinical suspicion of Silver-Russell syndrome (SRS). Methods: Following the international SRS consensus, methylation alterations and copy number variations (CNVs) at 11p15 region and maternal uniparental disomy of chromosome 7 were analysed and discarded by MS-MLPA. Results: Unexpectedly, the 11p15 region MS-MLPA showed a decrease in the signal of a copy number reference probe. Deletions affecting a single probe are inconclusive. So, we faced the ethical dilemma of whether it was appropriate to confirm this alteration with independent techniques and to offer a diagnostic possibility that was in no way related to clinical suspicion. Fortunately, in this particular case, the informed consent had not been specific to a particular pathology but to any disorder associated with growth failure. Performed alternative studies allowed the final diagnosis of 22q deletion syndrome. Conclusion: We demonstrate the importance of informing patients about the possibility of obtaining incidental findings in genetic techniques (not only in next generation sequencing) during pre-test genetic counselling consultations. In addition, we highlight the relevance of including in the informed consent the option of knowing these unexpected incidental findings as in some cases, this will help to elucidate the definitive diagnosis and provide the correct follow-up and treatment.

Genetic counseling processes and strategies for racially and ethnically diverse populations: A systematic review.

Genetic counseling outcomes are influenced by the processes and strategies used by counselors, yet little is known about how these strategies directly impact patients and populations. In particular, tailoring genetic counseling consultations to best meet the needs of cultural, racial, and ethnically diverse populations has been explored. This review aims to identify genetic counseling strategies tailored for a diversity of racial and ethnic populations with the goal to find ways to improve genetic counseling outcomes. Medline, Cochrane CENTRAL, Embase, PsychInfo, and CINAHL databases were searched for original research articles published in English that employed genetic counseling processes and strategies to improve genetic counseling outcomes, specifically for participants from ethnically or racially diverse populations. A review of 5300 titles and abstracts resulted in the identification of 36 articles that met the inclusion criteria. Three themes emerged: (1) community involvement in culturally tailoring genetic counseling, (2) creation and use of culturally tailored resources, and (3) modifications to the genetic counseling process. The effectiveness of genetic counseling strategies could not be evaluated due to lack of consistent outcome measures in the articles. The involvement of diverse ethnic and racial populations in developing inclusive genetic counseling tools and practices will help the profession provide better patient care in the future. More research connecting genetic counseling processes and outcomes will help to assess how well these modified approaches meet the needs of diverse populations.

Patient satisfaction, experience and preferences in the implementation of genetics teleconsultations in the North-eastern region of France

IntroductionIn France, few centres per region offer genetics consultations. Consequently, each centre covers a large area, often requiring patients to take a day off to travel long distances. In certain situations, genetic counselling in particular, a physical exam is not required. In these cases, teleconsultations between medical professional and patients, at the patient's location of choice, are an interesting offer. The COVID-19 pandemic has accelerated the implementation and the use of this type of consultation. With the aim of developing teleconsultation for certain types of referrals, a study of patient satisfaction, experience and preferences has been set up in our region. Methods2307 patients who had a teleconsultation by phone or videoconferencing with professionals from one of five genetic centres in North-eastern France between March and December 2020 were asked by e-mail or by post to answer an online survey. Results20% of the patients (n = 465) responded to the survey (80% women, 55% over 40 years old). In 64% of the cases (n = 299), the teleconsultation replaced a physical consultation due to the pandemic. In 56% of cases (n = 217), the consultations were conducted by videoconference. The teleconsultation involved the disclosure of results in 56% of cases (n = 260), a first consultation in 30% of cases (n = 138), and a follow-up consultation in 14% of cases (n = 67). The satisfaction rate was 96% (n = 447), with a rating of “excellent” in 72% of responses (n = 290) and “good” in 24% of responses (n = 157). Only 22% of the patients (n = 103), particularly patients who lived near the hospital or who were older than 70 years, would have preferred a physical consultation. Half of respondents (n = 232) declared that they avoided more than 1.5 h of transport, and 69% (n = 321) avoided taking a work day off. Patients were less often accompanied by a relative than if the consultation had taken place face-to-face (43%; n = 201 vs. 61%; n = 285). There was no change in responses during or after lock-down. ConclusionThis collection of feedback and analysis of patients’ preferences has validated the long-term implementation of medical genetics teleconsultations in certain circumstances and indications, for patients who prefer this approach.

Advancing precision oncology through systematic germline and tumor genetic analysis: The oncogenetic point of view on findings from a prospective multicenter clinical trial of 666 patients.

With the emergence of targeted therapies, there is a need to accurately identify more tumor biomarkers. The EXOMA trial was designed to offer tumor and germline exome sequencing (ES) to patients with solid malignant tumors and facing therapeutic failure. As hereditary cancer predispositions could be identified, with genetic counseling and health management implications, a genetic consultation was systematically established. This design needs to be discussed as genetic human resources are limited and indication of theranostic tests will increase. Genetic counseling was conducted within 15 days following inclusion in the study for patients recruited between December 2015 and July 2019. In silico analyses from theranostic ES were limited to 317 genes involved in oncogenesis, from both tumor and blood DNA. Six hundred and sixty six patients had a genetic consultation before ES. In 65/666 patients, 66 germline pathogenic or likely pathogenic (P/LP) variants were identified in 16 actionable genes and seven non-actionable genes according to French guidelines. 24/65 patients had previously received genetic analysis for diagnostic purposes, and for 17 of them, a P/LP variant had already been identified. Among the 48/65 remaining cases for which the EXOMA protocol revealed a previously unknown P/LP variant, only 19 met the criteria for genetic testing for inherited cancer risk after familial survey. These criteria had not been identified by the oncologist in 10 cases. In 21/65 cases, the variant was considered incidental. In 7.4% of patients, an undiagnosed hereditary genetic predisposition was identified, whether or not related to the clinical presentation, and germline analysis impacted oncological management for only 6.3% of the cohort. This low percentage should be weighed against the burden of systematic genetic consultation and urgent circuits. Information or training tools to form oncologists to the prescription of germline genetic analyses should be explored, as well as information supports and patient preferences.

The Role of the Neonatologist in Fetuses Diagnosed with Congenital Heart Disease.

Prenatal diagnosis of congenital heart disease (CHD) can decrease preoperative morbidity and mortality. Delivery room planning can improve cardiac hemodynamics and time to critical catheter and surgical interventions. Care algorithms have defined lesion-specific level-of-care assignments and delivery room action plans that can facilitate team-based approaches to safe deliveries. Neonatologists play critical roles in the care of fetuses diagnosed with CHD, from the time of diagnosis through the postnatal intensive care unit (ICU) stays. Prenatally, neonatologists are members of the multidisciplinary counseling teams, with expertise to counsel expectant parents about what to expect during the ICU stay, which is especially valuable in CHD associated with extracardiac or genetic anomalies. Neonatologists' role in delivery planning includes identification of the optimal delivery location and allocation of appropriate personnel and resources. After delivery, postnatal care considerations include hemodynamic stability, optimization of end-organ function, genetics consultation, developmentally appropriate care practices to encourage caregiver bonding, and optimization of care to improve neurodevelopmental outcomes of neonates with CHD.

Current State of Dor Yeshorim, Expanded Carrier, and Newborn Screening: Benefits and Limitations.

Availability and accessibility of preconception and prenatal genetic carrier and newborn biochemical and genetic screening have grown exponentially over the past 2 decades and as such, it is challenging for clinicians to keep pace. Although genetic counseling or genetic consultation should be offered to all expectant and new parents for prenatal screening decisions and positive results, benefits and limitations of these tests and results must be known and familiar to perinatal and pediatric clinicians. A brief historical overview of Dor Yeshorim, preconception and prenatal expanded carrier, and newborn screening is presented, followed by discussion about the conditions screened and considerations surrounding the benefits and limitations of these tests in the practice setting.

Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome

ObjectivesLong QT syndrome (LQTS) is one of the primary causes of sudden cardiac death (SCD) in youth. Studies have identified mutations in ion channel genes as key players in the pathogenesis of LQTS. However, the specific etiology in individual families remains unknown.MethodsThree unrelated Chinese pedigrees diagnosed with LQTS or Jervell and Lange-Nielsen syndrome (JLNS) were recruited clinically. Whole exome sequencing (WES) was performed and further validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing.ResultsAll of the probands in our study experienced syncope episodes and featured typically prolonged QTc-intervals. Two probands also presented with congenital hearing loss and iron-deficiency anemia and thus were diagnosed with JLNS. A total of five different variants in KCNQ1, encoding a subunit of the voltage-gated potassium channel, were identified in 3 probands. The heterozygous variants, KCNQ1 c.749T > C was responsible for LQTS in Case 1, transmitting in an autosomal dominant pattern. Two patterns of compound heterozygous variants were responsible for JLNS, including a large deletion causing loss of the exon 16 and missense variant c.1663 C > T in Case 2, and splicing variant c.605-2 A > G and frame-shift variant c.1265del in Case 3. To our knowledge, the compound heterozygous mutations containing a large deletion and missense variant were first reported in patients with JLNS.ConclusionOur study expanded the LQTS genetic spectrum, thus favoring disease screening and diagnosis, personalized treatment, and genetic consultation.

Identification of a novel CNV at the APC gene in a Chinese family with familial adenomatous polyposis.

Introduction: Familial adenomatous polyposis (FAP) is the second most commonly inherited colorectal cancer (CRC) predisposition caused by germline mutations within the adenomatous polyposis coli (APC) gene. The molecular defects and clinical manifestations of two FAP families were analyzed, and individual prevention strategies suitable for mutation carriers in different families were proposed. Methods and results: The pathogenic gene mutations were identified among the two families using whole-exome sequencing and verified with Sanger sequencing or quantitative polymerase chain reaction (qPCR). One novel (GRCh37:Chr5: 112145676-112174368, del, 28,692bp) and a known (c.C847T:p.R283X) mutation in the APC gene were pathogenic mutations for FAP, according to the sequencing data and tumorigenesis pattern among the family members. The two mutations led to a premature translational stop signal, synthesizing an absent or disrupted protein product. Conclusion: Our findings expand the known germline mutation spectrum of the APC gene among the Chinese population. This reaffirms the importance of genetic testing in FAP. Genetic consultation and regular follow-ups are necessary for the individualized treatment of cancer-afflicted families with APC expression deficiency. Additional work is required to develop safe and effective chemotherapy and immunotherapy for FAP based on the mutation type.

Clients' and genetic counselors' perceptions of empathy in Japan: A pilot study of simulated consultations of genetic counseling.

The rapidly increasing availability of genetic testing is driving the acceleration of genetic counseling implementation. Empathy is important in medical encounters in general and forms a core component of a successful genetic counseling session; however, empirical evidence on empathy in genetic counseling is minimal. This study aimed to explore the perceptions of empathy in simulated genetic counseling consultations from the perspectives of clients and genetic counselors. Semi-structured interviews and interpersonal process recall were used with participants of simulated genetic counseling consultations to elicit their experiences of empathy. A constructivist grounded theory was used for data analysis. A total of 15 participants, including 10 clients and 5 genetic counselors, participated in 10 simulated counseling sessions. The genetic counselors attempted to demonstrate empathy and were sensitive toward detecting changes in clients. Meanwhile, the clients' perceptions represented their feelings and thoughts elicited through the counselors' empathic approaches. This was the first process study to examine empathy in simulated genetic counseling sessions. Our model of communication of empathy is a process in which counselors try to address implicit aspects of clients, and clients are provided with time and a safe place for introspection, which contributes to discussions on building good relationships with patients. There is also a suggestion of the utility of simulated consultations for healthcare providers to learn empathic communication.

Utilization of multiple genetic methods for prenatal diagnosis of rare thalassemia variants.

Background: Thalassemia is the most prevalent monogenic disorder caused by an imbalance between the α- and β-globin chains as a result of pathogenic variants in the α- or β-globin genes. Novel or complex structural changes in globin genes are major hurdles for genetic consulting and prenatal diagnosis. Methods: From 2020 to 2022, genetic analysis was performed on 1,316 families suspected of having children with thalassemia major, including 42 pregnant couples suspected of being thalassemia carriers with rare variants. Multiple techniques including multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, targeted next-generation sequencing, and single-molecule real-time (SMRT) sequencing were used to diagnose rare thalassemia. Results: The rate of prenatal diagnosis for rare thalassemia variants was 3.19% (42/1,316). The most prevalent alleles of α- and β-thalassemia are Chinese Gγ(Aγδβ)0and -- THAI deletion. In addition, ten rare complex genotypes include one Chinese Gγ(Aγδβ)0 deletion combined with HBG1-HBG2 fusion, two rare deletions at HBB gene (hg38, Chr11: 5224211-5232470, hg38, Chr11: 5224303-5227790), one complete 7,412bp fusion gene for anti-Lepore Hong Kong, two complex rearrangements of the α-globin gene cluster, two novel duplications, and two rare large deletions in the α-globin gene cluster. Conclusion: Accurate gene diagnosis for probands with combined molecular biology techniques is the key to prenatal diagnosis of rare thalassemia.

Bilateral Vocal Fold Paralysis in a Patient With Congenital MYOD1 Myopathy.

Congenital bilateral vocal fold paralysis (BVFP) is a rare but significant cause of morbidity in pediatric otolaryngology. The differential diagnosis is expansive, with common etiologies including birth trauma, brainstem neoplasms, and neurologic disorders. There are few known genetic causes of the condition. This report details the first known case of BVFP secondary to a genetic deficiency in MYOD1, a master transcriptional regulator of skeletal muscle cell specification. Genetics consultation and testing may be a useful adjunct in the workup of congenital BVFP and may help guide prognostication, additional workup, counseling, and clinical decision-making.

Polygenic risk scores in pharmacogenomics: opportunities and challenges-a mini review.

Pharmacogenomics (PGx) aims at tailoring drug therapy by considering patient genetic makeup. While drug dosage guidelines have been extensively based on single gene mutations (single nucleotide polymorphisms) over the last decade, polygenic risk scores (PRS) have emerged in the past years as a promising tool to account for the complex interplay and polygenic nature of patients' genetic predisposition affecting drug response. Even though PRS research has demonstrated convincing evidence in disease risk prediction, the clinical utility and its implementation in daily care has yet to be demonstrated, and pharmacogenomics is no exception; usual endpoints include drug efficacy or toxicity. Here, we review the general pipeline in PRS calculation, and we discuss some of the remaining barriers and challenges that must be undertaken to bring PRS research in PGx closer to patient care. Besides the need in following reporting guidelines and larger PGx patient cohorts, PRS integration will require close collaboration between bioinformatician, treating physicians and genetic consultants to ensure a transparent, generalizable, and trustful implementation of PRS results in real-world medical decisions.