[Letters to Editor: The risk for clinically significant copy number variants in pregnancies with two soft markers, Geriatriophobia - a new concept in the medical world in Israel].

Letters to Editor: The risk for clinically significant copy number variants in pregnancies with two soft markers, Geriatriophobia - a new concept in the medical world in Israel.

Dystrophinopathy patient data as a guide to interpretation of pregestational female population screening for DMD gene variants.

Pregestational population screening of healthy females for copy number variants in DMD gene has raised numerous challenges regarding the interpretation and disclosure of these findings. Our objective was to analyze data from a local dystrophinopathy patient database, in comparison to population screening results. Utilizing the "Little steps" association registry for children with dystrophinopathy, we classified genetic findings (out-of-frame, in-frame, or difficult-to-predict) in 231 DMD and 90 BMD male patients.

[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.

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.

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

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.

[MOH SCREENING FOR TBCD IN COCHIN JEWS: COLLABORATION BETWEEN MEDICAL, RESEARCH AND COMMUNITY MEMBERS IN ACHIEVING PUBLIC HEALTH GOALS].

PEBAT (Progressive Encephalopathy, Early-Onset, with Brain Atrophy and Thin Corpus Callosum) is a rare disease characterized by a significant and progressive, neurological deficit. The disease has autosomal recessive etiology and is caused by bi-allelic variants in the gene TBCD (Tubulin-Specific Chaperone D). In 2017 the disease was diagnosed in two sisters from Jewish Cochin ethnicity (originating in Karela in south India) in Israel.

A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies.

Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018-2020).

Colchicine treatment increases the risk for fetal chromosomal aberrations-an observational study and systematic literature review.

Objectives: To examine the risk for chromosomal aberrations in fetuses of colchicine-treated patients in a large cohort, and to perform a systematic literature review on the subject.

Methods: For the observational study, a retrospective search was performed through the Ministry of Health computerized database, for all invasive tests performed due to parental colchicine treatment over the years 2003-19. The rate of aberrant karyotypes in pregnancies exposed to colchicine was compared with a local cohort of 2752 normal pregnancies, yielding six (0.

Chromosomal Microarray Analysis Results From Pregnancies With Various Ultrasonographic Anomalies.

Objective: To examine chromosomal microarray analysis results in pregnancies with various ultrasonographic anomalies and to characterize the copy number variants in diverse fetal phenotypes.

Methods: We retrospectively examined chromosomal microarray analyses of amniocenteses performed nationwide as a result of fetal ultrasonographic anomalies (structural defects, fetal growth restriction, and polyhydramnios) between January 2013 and September 2017. The rate of abnormal chromosomal microarray findings was compared between the different phenotypes and with a previously described control population of 15,225 pregnancies with normal ultrasonographic findings.

The limited effect of information on Israeli pregnant women at advanced maternal age who decide to undergo amniocentesis.

Background: A primary goal of amniocentesis is the detection of trisomy 21 (Down syndrome- DS) in the fetus. This procedure involves a small risk of miscarriage. As the risk of DS increases with maternal age, screening tests (maternal serum triple test and others) and age are used to generate a risk assessment, and amniocentesis is offered to women with high risk.

A Priori Attitudes Predict Amniocentesis Uptake in Women of Advanced Maternal Age: A Pilot Study.

Amniocentesis is an invasive procedure performed during pregnancy to determine, among other things, whether the fetus has Down syndrome. It is often preceded by screening, which gives a probabilistic risk assessment. Thus, ample information is conveyed to women with the goal to inform their decisions.

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2.

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained.

Factors that affect the decision to undergo amniocentesis in women with normal Down syndrome screening results: it is all about the age.

Background: Risk for foetal Down syndrome (DS) increases as maternal age increases. Non-invasive screening (maternal serum triple test) for DS is routinely offered to pregnant women to provide risk estimates and suggest invasive amniocentesis for definitive pre-natal diagnosis to high-risk women.

Objective: We examined women's decision process with regard to pre-natal screening, and specifically, the degree to which they take into account triple serum screening results when considering whether or not to undergo amniocentesis.

BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening.

Purpose: BRCA genes are associated with hereditary breast and ovarian cancers. Guidelines worldwide currently recommend BRCA genetic testing in asymptomatic individuals only if they belong to "high-risk" families. However, population screening for BRCA1/2 may be the logical next step in populations with a high prevalence of founder mutations, such as Ashkenazi Jews.

The best marker combination using the integrated screening test approach for detecting various chromosomal aneuploidies.

Aims: To evaluate the cross-trimester multiple marker correlation and the minimum marker combination needed for detecting various chromosomal aneuploidies.

Materials And Methods: Parturient women with singleton pregnancies who underwent non-interventional sequential screening test and followed prospectively were recruited. They all underwent first trimester combined nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotrophin (f-betahCG), followed by second trimester measurement of unconjugated estriol (uE3), human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP).

Low maternal serum concentrations of human chorionic gonadotropin as part of the triple test screening: a follow-up study.

Objective: To determine whether low maternal serum concentrations of human chorionic gonadotropin (hCG) were associated with poor pregnancy outcome.

Methods: Between 1999 and 2000, 20,880 women underwent triple test screening in our hospital. The levels of hCG were detected by fluorescent immunoassay.

Are amniotic fluid alpha-fetoprotein levels influenced by the gender in twin pairs?

Objectives: To examine the assumption that amniotic fluid alpha-fetoprotein (AFAFP) levels are different in female and male twin fetuses.

Design: Amniotic fluid levels of AFP in pregnancies with female and male fetuses in gender-concordant and gender-discordant twins were compared. A t test of p < 0.

Tay-Sachs disease and HEXA mutations among Moroccan Jews.

Moroccan Jewry (N>750,000) is the only non-Ashkenazi Jewish community in which Tay-Sachs disease (TSD) is not extremely rare. Previous studies among Moroccan Jewish TSD families identified three HEXA mutations. In this study, extended to enzyme-defined and new obilgate TSD carriers, we found four additional mutations.