Exploring the human genomic landscape: patterns of common homozygosity regions in a large middle eastern cohort.

Regions of Homozygosity (ROH) typically reflect normal demographic history of a human population, but may also relate to cryptic consanguinity, and, additionally, have been associated with specific medical conditions. The objective of this study was to investigate the location, size, and prevalence of common ROH segments in a Middle Eastern cohort. This retrospective study included 13 483 samples collected from all Chromosomal Microarray analyses (CMA) performed using Single Nucleotide Polymorphism (SNP) arrays at the genetic clinical laboratory of Rabin Medical Center between 2017-2023 (primary data set). An additional replication cohort including 100 842 samples from another SNP array platform, obtained from Maccabi Health Organization, was analyzed. Common ROH locations were defined as those ROH locations involving 1% or more of the samples. A total of 66 710 ROH segments, involving 13 035 samples (96.7%) were identified in the primary data set. Of the 4069 cytogenetic ROH locations, 68 were identified as common. The prevalence of non-common ROH was relatively high in affected individuals, and for acrocentric chromosomes, chromosomes associated with common trisomies, and non-imprinted chromosomes. In addition, differences in common ROH locations were observed between the primary and the replication cohorts. Our findings highlight the need for population-specific guidelines in determining ROH reporting cutoffs, considering factors such as population-specific prevalence and testing platform differences. Future research with larger, varied cohorts is essential to advance understanding of ROH's associations with medical conditions and to improve clinical practices accordingly.

The value of routine hemoglobin level evaluation following elective cesarean section: Is it worthwhile?

OBJECTIVE: The aim of this study was to assess the usefulness of routine hemoglobin testing following elective and urgent cesarean section (CS) in patients without primary postpartum hemorrhage (PPH). METHODS: This retrospective cohort study included women who underwent vaginal delivery (VD), elective CS, and urgent CS at Carmel Medical Center from 2015 to 2020. Data were extracted from the obstetric database, excluding deliveries with PPH. Demographic and obstetric variables were recorded. Primary outcomes were the need for packed red blood cell transfusion. RESULTS: A total of 19 446 women were included, with five (0.3%) requiring a blood transfusion in the elective CS group, 27 (0.17%) in the VD group, and eight (0.4%) in the urgent CS group. Urgent CS was associated with a higher risk of blood transfusion, but there was no significant difference between elective CS and VD. Elective CS showed the lowest rates of post-delivery hemoglobin below 7 g/dL 1 (0.1%) compared to VD 16 (0.6%) and urgent CS 13 (0.7%). CONCLUSION: Routine postoperative hemoglobin testing following elective CS in asymptomatic patients without PPH appears unnecessary. This study supports reconsidering routine hemoglobin testing following elective CS, aligning with the goal of optimizing resource utilization while maintaining patient quality.

Regions of Homozygocity size patterns among diverse ethnic groups in Israel: Toward tailored diagnostic reporting thresholds.

Long contiguous stretches of homozygosity or regions of homozygosity (ROH) are frequently detected via microarray and sequencing technologies. However, consensus on the establishment of specific size cutoffs for reporting ROH remains elusive. This study aims to assess the Total ROH Percentages (TRPS) and size of ROH segments across different ethnic origins, exploring potential disparities and proposing tailored diagnostic thresholds. This retrospective study included 13,035 microarray analyses conducted between 2017 to 2023. ROH segments on autosomal chromosomes were retrieved, and samples lacking ROH segments were excluded. The cohort was categorized based on reported ethnic origins, and TRPS and ROH segment size were analyzed for each origin. Distinct TRPS values were noted among different ethnic groups, ranging from median 0.36% in Ethiopian Jewish cohort and up to 6.42% in the Bedouin population. Wide range of 99th percentiles of ROH segment size for various origins was noted, ranging from 10.6 to 51.5 Mb. A significant correlation between ROH segment sizes and TRPS was noted in each origin. Statistically significant differences in ROH segment sizes were noted between the Jewish and the Israeli Arab/Druze origins in TRPS from 1% to 9.99%, whereas extremities of low (0.11%-0.99%) and high (over 10%) TRPS yielded no significant differences. In conclusion, as fixed absolute size thresholds may overlook pathogenic segments in certain populations while generating excessive reports in others, tailored approaches to define ROH reporting thresholds can be considered to facilitate the accuracy and clinical relevance of genomic analyses.

The effect of opting-in versus opting-out forming on the rate of reported variants of questionable significance in prenatal microarray.

OBJECTIVE: To examine the effect of patient-selected opt-in versus opt-out option on the rate of reported variants of uncertain clinical significance (VOUS) and high-frequency low-penetrant (HFLP) findings in prenatal microarray testing. METHODS: A standard microarray consent form in Israel includes a requirement to note patient choice to be or not to be informed about the presence of VOUS and HFLP variants. The original form was designed as an opting-out method, in which the women had to actively mark if they did not want to be informed about questionable findings. In the authors' Genetic Institute, the form was changed for an opting-in option in October 2019. In this study we have compared the rates of reported VOUS and HFLP variants between the opt-in and opt-out periods. RESULTS: Of the 1014 prenatal CMA tests, 590 (58.2%) were performed in the opt-out period. A significant decrease in the rate of women requesting to be informed of VOUS findings was noted (66.8% in opt-out period vs 34.0% in opt-in period), yielding a relative risk (RR) of 0.46 (95% confidence interval [CI] 0.39-0.53). Rate of women preferring to be informed of HFLP variants decreased from 75.3% to 48.1% (RR 0.52, 95% CI 0.45-0.60). DISCUSSION: We present a simple and effective method to decrease the rate of reported findings of questionable significance in the prenatal setting. These results are important not only for microarray results, but also for next-generation sequencing techniques, such as whole exome or genome sequencing.

Compliance and satisfaction with BRCA surveillance in specialized clinics versus community follow-up.

OBJECTIVE: To assess adherence to medical follow-up protocols among BRCA1/2 carriers and compare outcomes between dedicated carrier clinics and community healthcare settings. METHODS: This cross-sectional study was conducted by distributing an anonymous questionnaire within the 'Good BRCA Genes - Support and Information Group for BRCA Carriers' association. The questionnaire assessed adherence to recommended surveillance and satisfaction with various aspects of the follow-up. RESULTS: Of the 682 BRCA carriers surveyed, 68.5% reported fully adhering to recommended medical follow-up. Those not fully adhering cited bureaucracy challenges, scheduling difficulties, timing uncertainties, and difficulty remembering examination dates. Less than 50% were satisfied with appointment availability, scheduling, contact persons, and general practitioners' knowledge of BRCA carrier risks and follow-up. The 417 women monitored in dedicated breast clinics reported notably higher optimal adherence to recommended surveillance (78.3 vs. 53.6%, P < 0.0001). In addition, they noted greater satisfaction with appointment availability (63.7 vs. 25.0%, P < 0.0001), appointment scheduling process (58.1 vs. 24.7%, P < 0.0001), availability of breast surgeons/gynecology specialists (67.4 vs. 50.8%, P < 0.0001), and availability of a contact person for consultations between appointments (53.5 vs. 20.8%, P < 0.0001). DISCUSSION: Our findings highlight the advantages of surveillance in dedicated BRCA1/2 clinics, including closer monitoring and increased satisfaction. Given the limited availability of such clinics and the growing number of BRCA1/2 carriers, the opening of additional dedicated clinics and the consideration of alternative surveillance-enhancing solutions, such as training healthcare professionals, using digital tools, and employing artificial intelligence, are essential.

[THE RISK FOR CLINICALLY SIGNIFICANT COPY NUMBER VARIANTS IN PREGNANCIES WITH TWO SOFT MARKERS].

INTRODUCTION: Soft sonographic markers, such as an intracardiac echogenic focus, are demonstrated in one out of 150 live births and are associated with a slightly increased risk of trisomy 21 and 18. In the case of an isolated soft marker, the recommendation to perform invasive tests such as amniocentesis or placental cyst testing depends to a large extent on the results of biochemical first and second trimester maternal serum screening. In the case of two soft markers, the women are referred to genetic counseling, and invasive testing is funded by the Ministry of Health. OBJECTIVES: To estimate the risk for clinically significant copy number variants (CNVs) in pregnancies with two soft markers. METHODS: This retrospective cohort study included all prenatal microarray tests performed during 2013-2021, due to demonstration of two soft markers (namely: echogenic intracardiac foci, choroid plexus cyst, single umbilical artery and mild pyelectasis). The rates of clinically significant (pathogenic and likely pathogenic) microarray findings were compared to a previously published cohort of 7235 pregnancies with normal ultrasound, in which 87 (1.2%) abnormal CNVs were noted. RESULTS: Of the 150 pregnancies with two soft markers, two (1.3%) clinically significant CNVs were found. The rate of abnormal microarray findings did not differ from baseline risk in pregnancies with normal ultrasound - relative risk of 1.11 (95% confidence interval 0.28-4.40). CONCLUSIONS: The risk for abnormal microarray findings in pregnancies with two soft markers was not significantly increased in comparison to control group of pregnancies with normal sonography. DISCUSSION: These results undermine the current national policy of genetic counseling and Ministry of Health-funded invasive testing in pregnancies with a combination of two soft markers. These findings are important for additional countries with similar management, and may facilitate the genetic counseling and informed decision-making in such cases.

[THE EFFECTS OF GENDER ON THE MANIFESTATIONS AND CONSEQUENCES OF WEIGHT STIGMA].

INTRODUCTION: Weight stigma, or weight bias, refers to biased beliefs and negative opinions towards people with excess weight. This phenomenon manifests in prejudice and negative attitudes towards people with obesity, including disrespectful treatment, bullying, discrimination and even abuse, and leading to long-term negative consequences on physical and mental health. The purpose of the current review was to examine the relationship between gender and manifestations of weight stigma. Studies listed in this review show that the phenomenon of weight stigma is more common and severe among women, in numerous life areas, which include education, employment, the healthcare system, social media, sports industry, and interpersonal relationships. Possible reasons for such differences include the existing discrimination against women in various areas of life, and the emphasis on external appearance and the ideal of thinness, which relates mainly to women. In light of the serious consequences of weight stigma on public health and individual well-being, efforts must be made to prevent weight stigma, including the education of the general population, changing policies of healthcare, education and media systems, and legislation to prevent weight-based discrimination.

The association between BMI, episiotomy, and obstetric anal sphincter injuries (OASIS) in singleton vaginal deliveries.

OBJECTIVE: Prevalence of obesity in reproductive age and pregnant women has been on the rise during the past several decades. The relationship between body mass index (BMI) and obstetric anal sphincter injuries (OASIS) or episiotomy has not yet been thoroughly investigated. The objective of this study was to shed light on this issue. METHODS: This retrospective cohort study was performed using electronic database of an obstetrics department at a university-affiliated tertiary medical center. All spontaneous singleton vaginal deliveries at term between January 2015 and December 2021 were included. The primary outcome was the incidence of OASIS (third- and fourth-degree perineal tears) and obesity. These were compared across three BMI categories: normal (BMI below 25 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI of 30 kg/m2 and over). RESULTS: Of the overall 13,932 spontaneous vaginal deliveries identified, 34.7 % had BMI in the normal range, 43.1 % were overweight, and 25.4 % were obese. Multivariate analysis demonstrated lower rates of OASIS in obese (OR 0.2, 95 %CI 0.04-0.9) and in overweight (OR 0.3, 95 %CI 0.1-0.99) women, as compared to the normal-weight cohort. In addition, lower rates of episiotomy were noted in the obese cohort (OR 0.7, 95 %CI 0.6-0.8). CONCLUSIONS: Decreased incidence of OASIS was noted in women with obesity, in conjunction with lower use of episiotomy. These findings imply that obstetrics clinics might consider a more conservative approach to episiotomy in obese patients.

Impact of body mass index and examination type on utilization of screening programs: A big data study.

OBJECTIVE: To investigate the relationship between Body Mass Index (BMI) and adherence to recommended screening tests, addressing gaps in previous literature by utilizing a large cohort, while considering longitudinal changes in weight and the type of screening. METHODS: Data from Clalit Health Services in Israel were retrospectively analyzed, including participants aged 50 and above from 2002 to 2021. BMI measurements and various screening test records were examined. Generalized Estimating Equations were employed for analysis, adjusting for potential confounding variables, including age, gender, geographic location, and socioeconomic status. RESULTS: The study included 634,879 participants with 4,630,030 BMI measurements and 56,453,659 test records. Participants were categorized into BMI cohorts at the time of the test, with overweight and obese individuals showing lower odds of undergoing intimate examination-based screening tests (mammography, PAPS, and skin examination), as opposed to higher odds of several non-intimate tests (e.g., diabetes and eye disorder screenings). DISCUSSION: Our findings suggest that individuals with overweight and obesity are less likely to undergo screenings involving intimate physical examinations, potentially due to weight stigma and discomfort. This avoidance behavior may contribute to increased morbidity rates in these populations. Interventions addressing weight stigma, improving access to care, and enhancing patient engagement are warranted.

Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases.

BACKGROUND: Distal Xq28 duplication, or int22h1/int22h2-mediated Xq28 duplication syndrome, leads to cognitive impairment, neurobehavioral issues, and facial dysmorphisms. Existing literature has limited information on clinical traits and penetrance. METHODS: We identified cases of distal Xq28 duplication (chrX: 154,126,575-154,709,680, GRCh37/hg19) through a review of clinical records and microarray reports from five centers, encompassing both postnatal and prenatal cases, with no prior family knowledge of the duplication. RESULTS: Our search found 47 cases across 26 families, with duplications ranging from 208 to 935 Kb. In total, 8 out of 26 index cases featured a 200-300 kb partial duplication, mainly from Armenian/Caucasian Jewish backgrounds. Most prenatal cases showed no major fetal ultrasound malformations. Of cases with known inheritance mode (15 out of 26), maternal inheritance was more common (80%). The study identified seven male carriers of the duplication from six unrelated families, indicating partial penetrance in males. CONCLUSION: Our study provides key insights into distal Xq28 duplication. Most prenatal tests showed no major fetal ultrasound issues. Maternal inheritance was common, with unaffected mothers. In the postnatal group, a balanced gender distribution was observed. Among male family members, two fathers had ADHD, one was healthy, and one brother had mild symptoms, indicating partial penetrance in males.

Exploring the factors affecting classification and reporting of uncertain prenatal microarray findings, using a "virtual fetus" model-a pilot study.

OBJECTIVE: Significant discrepancy exists between laboratories in classification and reporting of copy number variants (CNVs). Studies exploring factors affecting prenatal CNV management are rare. Our "virtual fetus" pilot study examines these factors. METHOD: Ten prenatally diagnosed CNVs of uncertain significance (VUS) > 1Mb, encompassing OMIM-morbid genes, inherited from healthy parents, were classified by 15 MD geneticists from laboratory, prenatal, and preimplantation genetic testing (PGT) units. Geneticists addressed factors affecting classification, obligation to report, and recommendation for invasive testing or PGT. RESULTS: CNVs were classified likely benign (10.7%), VUS (74.7%), likely pathogenic (8.7%), or pathogenic (6.0%). Classification discrepancy was higher for losses versus gains. Classifying pathogenic/likely pathogenic was more common for losses (adjusted odds ratio [aOR] 10.9, 95% CI 1.55-76.9), and geneticists specializing in gynecology (aOR 4.9, 95% CI 1.03-23.3). 84.0% of respondents would report CNVs, depending on classification and family phenotype. Invasive testing in pregnancies was recommended for 29.3% of CNVs, depending on the classification and geneticist's specialization. PGT was recommended for 32.4%, depending on classification, experience years, and family's phenotype (38.0% for patients undergoing in vitro fertilization irrespectively, 26.7% otherwise). CONCLUSION: Factors affecting CNV classification/reporting are mainly dosage, family phenotype, geneticist specialization and experience. Understanding factors from our pilot study may facilitate developing an algorithm for clinical consensus and optimal management.

"We hear and we fear" - Insights of 1203 Women on Personnel Conversations During Cesarean Delivery.

OBJECTIVE: To assess the preferences of women undergoing cesarean delivery regarding intraoperative conversations among healthcare personnel. METHODS: This cross-sectional study was conducted by distribution of an open anonymous questionnaire on social media platforms during March 2022, targeting respondents with a history of cesarean delivery. The primary outcome was patients' experience of "being disturbed by professional and casual conversations of the personnel", rated on a 1-5 Likert scale. RESULTS: 1203 participants completed the questionnaire, with 97.6% reporting intraoperative conversations among personnel. Casual conversations were perceived as "disturbing" by more respondents vs. professional talk (33.4% vs. 27.6%, respectively, p = 0.0077). Logistic regression analysis revealed associations between feeling disturbed and higher intraoperative stress and pain - adjusted Odds Ratio (OR) 3.1, 95% confidence interval (CI) 2.1-4.5, and OR 2.7, 95%CI 1.8-4.0, respectively, for professional conversations; OR 3.0, 95%CI 2.0-4.4, and OR 1.7, 95%CI 1.1-2.7, respectively, for casual conversations. Feeling disturbed by professional conversations was also associated with urgent vs. elective operations (OR 2.0, 95%CI 1.4-3.0). Direct personnel-patient communication was associated with significantly lower stress levels (60.8% vs. 72.5% in the remaining cohort, p < 0.001). DISCUSSION: Intraoperative conversations of the personnel occur during vast majority of cesarean deliveries. Given that a substantial proportion of patients find these conversations disturbing, it is advisable to conduct a preliminary assessment of maternal preferences. This proactive step can help tailor communication strategies to individual patient comfort and preferences, ultimately enhancing the birthing experience and maternal well-being.

The association between obesity and the success of trial of labor after cesarean delivery (TOLAC) in women with past vaginal delivery.

OBJECTIVES: To evaluate the effect of overweight (body mass index; BMI 25.0-29.9 kg/m2), and obesity (BMI>30 kg/m2), on the success of trial of labor after cesarean delivery (TOLAC), with consideration of successful past vaginal birth. METHODS: This retrospective cohort study was performed using electronic database of obstetrics department at a university-affiliated tertiary medical center. All women admitted for TOLAC at 37-42 weeks of gestational age, carrying a singleton live fetus at cephalic presentation, with a single previous low segment transverse cesarean delivery between 1/2015 and 5/2021 were included. Primary outcome was the rate of cesarean delivery during labor, and subgroup analysis was performed for the presence of past vaginal birth. RESULTS: Of the 1200 TOLAC deliveries meeting the inclusion criteria, 61.9 % had BMI in the normal range, 24.6 % were overweight (BMI 25.0-29.9 kg/m2), and 13.4 % were obese (BMI of 30 kg/m2 and over). Using a multivariate analysis, BMI≥30 kg/m2 was associated with increased risk of cesarean delivery compared to normal weight. However, in the subgroup of 292 women with a history of successful vaginal birth BMI did not affect TOLAC success. CONCLUSIONS: BMI does not affect the success of TOLAC in women with previous vaginal birth. This information should be considered during patients counselling, in order to achieve a better selection of mode of delivery and higher patients' satisfaction.

Prevalence of high-penetrant copy number variants in 7734 low-risk pregnancies.

BACKGROUND: The rate of clinically significant copy number variants in chromosomal microarray analysis in low-risk pregnancies is approximately 1%. However, these results include copy number variants with low and variable penetrance, although some patients might be interested only in the detection of high-penetrant variants. OBJECTIVE: This study aimed to calculate the prevalence of high-penetrant copy number variants in a large cohort of low-risk pregnancies. STUDY DESIGN: This retrospective study was performed using microarray results of pregnancies with normal ultrasound and maternal serum screening. All clinically significant (pathogenic and likely pathogenic) copy number variants were recorded. Of these, only high-penetrant findings were selected. Findings with low and medium penetrance and copy number variants with unknown clinical penetrance, including uniparental disomy of segments not related to known imprinted syndromes, mosaic aneuploidy of <50%, and segmental mosaicism, were excluded. The calculation was performed for the overall cohort, for women aged >35 years and women aged <35 years, and after omission of noninvasive prenatal screening theoretically detectable findings (trisomies 13, 18, and 21). RESULTS: Clinically significant copy number variants were detected in 118 of 7734 cases (1.50% or 1:65), and high-penetrant copy number variants were detected in 33 of 7734 cases (0.43% or 1:234). In women aged ≥35 years, the rates of high-penetrant copy number variants were 29 of 5734 cases (0.51% or 1:198) and 4 of 2000 cases (0.20% or 1:500) in women aged <35 years (P=.0747). Following the omission of 12 theoretically noninvasive prenatal screening-detectable findings, the rates of high-penetrant copy number variants declined to 21 of 7722 cases (0.27% or 1:368) in the whole cohort-18 of 5723 cases (0.31% or 1:318) in woman aged ≥35 years and 3 of 1999 cases (0.15% or 1:666) in younger women (P=.319). CONCLUSION: The risk of high-penetrant copy number variants in low-risk pregnancies exceeds the risk of miscarriage after invasive testing, even after normal noninvasive prenatal screening results. These results are of importance to genetic counselors and obstetricians, to facilitate maternal informed decision-making when considering invasive prenatal testing in low-risk pregnancies.

Lessons learned from the first national population-based genetic carrier-screening program for Duchenne muscular dystrophy.

PURPOSE: To summarize the results of first year implementation of pan-ethnic screening testing for Duchenne muscular dystrophy (DMD) and present the ensuing challenges. METHODS: Data acquisition for this study was performed by retrospective search of Ministry of Health registry for reports of all laboratories performing genetic screening tests. DMD testing was performed by multiplex ligation-dependent probe amplification technology. In case of single-exon deletion, sequencing of the specific exon was performed to rule out underlying single-nucleotide variant. RESULTS: Of overall 85,737 DMD tests, 82 clinically significant findings were noted (0.095%, or 1:1,046 women). In addition, 80 findings with uncertain clinical significance were detected (0.093%, or 1:1072), as well as 373 cases (0.4%, or 1:230) of single-exon deletions subsequently identified as false positives because of underlying single-nucleotide variant, mostly variants in exon 8 in North African Jewish population, and in exon 48 in Arab Muslim population. CONCLUSION: Interpretation of population-based DMD carrier screening is complex, occasionally requiring additional genetic testing methods and ethical considerations. Multicenter data registry, including ethnic origin and familial segregation in selected cases, is crucial for optimal definition of the results during genetic counseling and informed decisions regarding prenatal testing.

[ADVANCES AND CHALLENGES IN THE FIELD OF GENETIC TESTING - AN INTRODUCTORY ARTICLE].

INTRODUCTION: In the current issue of Harefuah, we present original research articles and reviews, reflecting the tremendous development of the field of genetic testing. This progress provides extensive tools for determining genetic diagnoses, thereby enabling detailed explanation for patients and their family members regarding the specific genetic disorder, adjustment of medical evaluation and follow-up, and allowing informed decision-making during pregnancy. Furthermore, there are advances in the assessment of recurrence of risks among members of the extended family, including future pregnancies, with a possibility of prenatal diagnosis and pre-implantation genetic testing.

[CHARACTERIZATION OF THE INDICATIONS FOR PERFORMING GENE PANEL SEQUENCING TESTS IN A GENOMIC CENTER].

INTRODUCTION: Following the recent human genome revolution, novel technologies have been developed in the last decade enabling advanced sequencing tests, including genetic panel tests that focus on groups of specific genes associated with a certain medical condition (phenotype). Since the process of assembling a genetic panel may be complex and requires significant manpower and time, it is important to define the most common and requested panels, for gradual construction and introduction of panel tests starting with the most common. AIMS: Since no information was found in the literature defining the common panels, the aim of the study was to define the indications for performing a gene panel within the framework of the provided services, and to estimate their frequency. METHODS: Prospective data acquisition was performed by a party responsible for approval of panel tests within Clalit Health Services Organization. The indications for all approved panel tests were registered since the launch of Clalit's Genomic Center. The total number of indications was counted, and according to the Pareto principle, 20% of the most frequent indications were chosen. In addition, the indications were divided into main medical disciplines. RESULTS: Overall, 132 indications were recorded for approved gene panel tests; 20% of these indications, i.e. the first 26 indications in terms of frequency, covered 79.6% of the cases. The most frequent approved panels were epilepsy (10.4%, confidence interval (CI) 8.5-12.6%), Maturity-onset diabetes of the young (MODY) (9.6%, CI 7.8-11.7%), cardiomyopathy (8.3%, CI 6.6-10.3%) and hearing impairment (7.6%, CI 6.0-9.6%). The most common disciplines in descending order were neurological diseases (23.0%, CI 20.3-25.9%), endocrinology (13.1%, CI 11.1-15.6%), heart diseases (9.0%, CI 7.3-11.1%) and eye diseases (7.8%, CI 6.2-9.8%). CONCLUSIONS: A review of panel approvals at the Genomic Center of Clalit showed a number of frequent indications. DISCUSSION: We believe this information can be useful for the establishment of genomic laboratories, as well as for the improvement of the service to the patients, by enabling the referral for specific panel tests by medical experts who are not geneticists or genetic counselors, after appropriate training (such as the "Genetics First" program of Clalit).

[HOW SIMPLE IS "SIMPLE" GENETIC COUNSELING?]

INTRODUCTION: Genetic counselors are often compared with other medical professionals in terms of productivity, based on the number of patients seen and the time required for each patient. Prenatal genetic counseling before amniocentesis in uneventful pregnancies is considered to be a "simple" counseling, with potentially less time required for each patient. Thus, in some medical centers the duration of such consultations is limited to provide only the basic explanation without detailed collection of personal and family history, while in others the explanation is given to several patients together. AIMS: To assess the need for extended genetic counseling during supposedly "simple" genetic consultations before amniocentesis. METHODS: Data was collected from January 2018 until August 2020 of all patients undergoing genetic counseling before amniocentesis due to advanced maternal age, abnormal biochemical screening, or without medical indication. The consultations were given by four genetic counselors and two medical geneticists. The need for extended genetic counseling was evaluated based on pedigree and the discussion summaries and recommendations noted in genetic counseling summaries. RESULTS: Of the 1085 relevant counseling appointments, 657 (60.5%) required additional explanation beyond the basic consultation. The reasons for extended counseling included medical disorders of the woman or spouse (21.2%), carrier state for autosomal recessive diseases (18.6%), diagnosed or suspected genetic conditions of a child or previous pregnancy (9.6%), or medical disorders in the extended family (79.1%). In 31.0% of patients, recommended carrier screening tests were recommended or added. In 32.3% of cases, only one extra subject was counseled, in 16.3% two subjects, and in 5%, three subjects or more. The additional explanations were estimated as short (up to 5 minutes) in 36.9% of the cases, intermediate (5 to 15 minutes) in 59.9%, and long (over 15 minutes) in 2.6% of cases. The consultation's duration was not affected from it being a first meeting or a recurrent consultation. CONCLUSIONS: The need for further explanation was demonstrated in over 60% of genetic consultations, performed prior to amniocentesis due to supposedly "simple" indication. DISCUSSION: This fact reflects the importance of formal genetic counseling even in cases of seemingly simple indications, with an emphasis on detailed personal and family history, dedicating sufficient time to the counseling itself. Alternatively, it is important to exercise extra caution when conducting a short explanatory conversation prior to amniocentesis, including detailed questionnaires and the patient's signature on the possible limitations of such explanations.

[SUMMARY AND UPDATES IN THE FIELD OF GENETIC TESTING IN ISRAEL - AS OF 2022].

INTRODUCTION: Considerable progress has been observed in the field of genetic counseling and testing in Israel, including the availability and funding of services. The purpose of the article is to summarize the management and present the updates in the field of genetic testing in Israel, as of 2022. The progress in the field of pregnancy-related genetic testing includes an ancestry-based annually updated genetic screening, which has significantly reduced the incidence of several severe and common hereditary diseases. A comprehensive and uniform genetic screening test was submitted for approval by the next basket committee.