Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy.

The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8.

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.

Loss of function of FIGNL1, a DNA damage response gene, causes human ovarian dysgenesis.

Ovarian dysgenesis (OD), an XX disorder of sex development, presents with primary amenorrhea, hypergonadotrophic hypogonadism, and infertility. In an Ashkenazi Jewish patient with OD, whole exome sequencing identified compound heterozygous frameshifts in FIGNL1, a DNA damage response (DDR) gene: c.189del and c.

[GENOTYPE-PHENOTYPE CORRELATIONS BY SPECIFIC FOUNDER VARIANTS IN BRCA IN ISRAELI WOMEN].

Introduction: Hereditary breast and ovarian cancer (HBOC) is predominantly accounted for by pathogenic variants (PVs) in BRCA1/BRCA2 genes. Population screening for recurring PVs in Ashkenazi Jews (AJ) was incorporated into the Israeli health basket in 2020, increasing the identification of BRCA carriers. Information on cancer risks for each PV in Israel is limited.

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal.

Cytomegalovirus (CMV) seroprevalence among women at childbearing age, maternal and congenital CMV infection: policy implications of a descriptive, retrospective, community-based study.

Background: Maternal CMV infection during pregnancy, either primary or non-primary, may be associated with fetal infection and long-term sequelae. While guidelines recommend against it, screening for CMV in pregnant women is a prevalent clinical practice in Israel. Our aim is to provide updated, local, clinically relevant, epidemiological information about CMV seroprevalence among women at childbearing age, the incidence of maternal CMV infection during pregnancy and the prevalence of congenital CMV (cCMV), as well as to provide information about the yield of CMV serology testing.

Repeat low order caesarean delivery, risk factors for complications: A retrospective, longitudinal study.

One-third of cesarean deliveries (CDs) are repeat operations, of which the majority are low-order, second (CD2) and third (CD3). The study objectives were to identify risk factors for a complicated maternal CD among women undergoing a repeat low-order CD and to develop a predictive model for at-risk women. A retrospective longitudinal follow-up study was conducted in a single medical center, during 2005-2016.

Trial of labor following cesarean in preterm deliveries: success rates and maternal and neonatal outcomes: a multicenter retrospective study.

Purpose: To evaluate the rates of vaginal birth after cesarean (VBAC) among parturients attempting preterm trial of labor following a cesarean delivery (TOLAC) vs. term TOLAC.

Methods: A multicenter historic cohort study was conducted at two university-affiliated centers between August 2005 and March 2021.

Use of antibiotics in women undergoing correction of an obstetric anal sphincter injury: Results from a national Israeli survey.

Objective: Obstetric anal sphincter injures (OASIS) have long-term implications on women's health. Administration of antibiotic prophylaxis and treatment following OASIS repair is controversial. We conducted a national survey to provide data about practice routines regarding antibiotic prophylaxis and treatment following OASIS repair in Israeli labor and delivery units.

Combining cytogenetic and genomic technologies for deciphering challenging complex chromosomal rearrangements.

Complex chromosomal rearrangements (CCRs), a class of structural variants (SVs) involving more than two chromosome breaks, were classically thought to be extremely rare. As advanced technologies become more available, it has become apparent that CCRs are more common than formerly thought, and are a substantial cause of genetic disorders. We attempted a novel approach for solving the mechanism of challenging CCRs, which involve repetitive sequences, by precisely identifying sequence-level changes and their order.

A recessive S174X mutation in Optineurin causes amyotrophic lateral sclerosis through a loss of function via allele-specific nonsense-mediated decay.

Loss of function (LoF) mutations in Optineurin can cause recessive amyotrophic lateral sclerosis (ALS) with some heterozygous LoF mutations associated with dominant ALS. The molecular mechanisms underlying the variable inheritance pattern associated with OPTN mutations have remained elusive. We identified that affected members of a consanguineous Middle Eastern ALS kindred possessed a novel homozygous p.

Breast cancer risk and hormone replacement therapy among BRCA carriers after risk-reducing salpingo-oophorectomy.

Introduction: BRCA1/BRCA2 mutation carriers often undergo risk-reducing salpingo-oophorectomy (RRSO) before natural menopause, raising the issue of hormonal replacement treatment (HRT) use. There is conflicting evidence on the effect of HRT on breast cancer (BC) risk, and there are limited data on risk based on age at exposure. In the general population, HRT users have an increased BC risk (hazard ratio = 1.

The Yield of Chromosomal Microarray in Pregnancies Complicated with Fetal Growth Restriction Can Be Predicted According to Clinical Parameters.

Introduction: We evaluated the yield of chromosomal microarray analysis in pregnancies complicated with fetal growth restriction (FGR) according to specific clinical parameters.

Methods: The study was based on national records from the Israeli Ministry of Health. Chromosomal microarray analyses of amniocenteses performed nationwide for the indication of FGR, from January 2016 to March 2018, were included.

Age at diagnosis of cancer in 185delAG BRCA1 mutation carriers of diverse ethnicities: tentative evidence for modifier factors.

Germline pathogenic sequence variants (PSVs) in BRCA1 substantially increase risk for developing breast (BC) and ovarian cancer (OvC). Yet, incomplete penetrance suggests that modifier factors affect phenotypic expression of mutant BRCA1 alleles. Analysis of identical BRCA1 PSV carriers of diverse ethnicities may provide further evidence for modifier factors.

Chromosomal microarray should be performed for cases of fetal short long bones detected prenatally.

Purpose: To investigate the prevalence of pathogenic and likely-pathogenic variants detected by chromosomal microarray analysis (CMA), among pregnancies with fetal short long bones diagnosed by ultrasound.

Methods: The study cohort was based on cases of chromosomal microarray analyses performed nationwide for the indication of short long bones.

Results: CMA was performed in 66 cases of short long bones.

Teaching clinicians practical genomic medicine: 7 years' experience in a tertiary care center.

Purpose: Increased implementation of complex genetic technologies in clinical practice emphasizes the urgency of genomic literacy and proficiency for medical professionals. We evaluated our genomic education model.

Methods: We assessed the 5-day, extended format program, encompassing lectures, videos, interactive tests, practice cases, and clinical exercises.

Prolonged operative time of repeat cesarean is a risk marker for post-operative maternal complications.

Background: Repeat cesarean delivery (CD) accounts for approximately 15% of all annual deliveries in the US with an estimated 656,250 operations per year. We aimed to study whether prolonged operative time (OT; skin incision to closure) is a risk marker for post-operative maternal complications among women undergoing repeat CD.

Methods: We conducted a cross-sectional retrospective study in a single tertiary center including all women who underwent repeat CD but excluding those with cesarean hysterectomy.

Uterine cancer in Jewish Israeli BRCA1/2 mutation carriers.

Background: BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved.

Method: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited.

Screening for germline mutations in breast/ovarian cancer susceptibility genes in high-risk families in Israel.

We evaluated the clinical utility of screening for mutations in 34 breast/ovarian cancer susceptibility genes in high-risk families in Israel. Participants were recruited from 12, 2012 to 6, 2015 from 8 medical centers. All participants had high breast/ovarian cancer risk based on personal and family history.

Intrapartum fetal heart rate patterns of trisomy 21 fetuses: A case-control study.

Background/aim: To determine whether there are specific characteristic intrapartum heart rate patterns for fetuses with trisomy 21(T21).

Background Study Design/patients: Intrapartum fetal heart rate (FHR) tracings of T21 fetuses were compared to those of euploid fetuses in a retrospective, observational, matched, case-control study. The study group consisted of 42 fetuses with T21 and 42 matched euploid controls.