Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1.

Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness-associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity.

Based on a cohort of 52,879 microarrays, recurrent intragenic FBN2 deletion encompassing exons 1-8 does not cause Beals syndrome.

Introduction: Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder, associated with heterozygous mutations in the FBN2 gene. The objective of this study was to evaluate the prevalence of an intragenic deletion encompassing exons 1-8 of FBN2 gene in Israeli population.

Materials And Methods: A search for intragenic FBN2 microdeletions was performed in two databases of chromosomal microarray analysis (CMA) - genetic laboratory of a tertiary medical center (the primary cohort) and one of the largest Israeli health maintenance organizations (replication cohort).

Yemenite-Jewish families with Machado-Joseph disease (MJD/SCA3) share a recent common ancestor.

In 1994, a kindred from Yemen was described as the first Jewish family with Machado-Joseph disease (MJD/SCA3), a dominant ataxia caused by the expansion of a (CAG) above 61 repeats, in ATXN3. MJD is spread worldwide due to an ancient variant of Asian origin (the Joseph lineage). A second, more recent, independent expansion arose in a distinct haplotype (Machado lineage); other possible origins are still under study.

Chromosomal microarray findings in pregnancies with an isolated pelvic kidney.

Objective To examine the risk for abnormal chromosomal microarray analysis (CMA) results among fetuses with an apparently isolated pelvic kidney. Methods Data from all CMA analyses performed due to an isolated pelvic kidney reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained. Risk estimation was performed comparing the rate of abnormal observed CMA findings to the general population risk, based on a systematic review encompassing 9272 cases and on local data of 5541 cases.

Ophthalmic manifestations of Heimler syndrome due to PEX6 mutations.

Background/aims: Pigmentary retinal dystrophy and macular dystrophy have been previously reported in Heimler syndrome due to mutations in PEX1. Here we reported the ocular manifestations in Heimler syndrome due to mutations in PEX6.

Materials And Methods: Medical records were reviewed to identify patient demographics, ophthalmic and systemic findings, and results of diagnostic testing including whole genome sequencing.

Non-visualization of fetal gallbladder in microarray era - a retrospective cohort study and review of the literature.

Objective: The objective of this study is to examine the frequency of abnormal Chromosomal Microarray (CMA) analyses among fetuses with isolated non-visualization of fetal gallbladder.

Methods: Data from CMA analyses performed due to isolated non-visualization of fetal gallbladder between January 2013 and September 2016 were retrospectively acquired from a computerized database of the Israeli Ministry of Health. The results were compared with the rate for clinically significant CMA findings in general population, based on a large cohort of 5541 pregnancies undergoing CMA due to maternal request, and a systematic review of 9272 cases with normal ultrasound.

The association between maternal serum first trimester free βhCG, second trimester intact hCG levels and foetal growth restriction and preeclampsia.

The purpose of this study was to analyse the association between free beta hCG (fβhCG) increased levels and pregnancy complications (PC), foetal growth restriction (FGR) and preeclampsia (PE). This connection was evaluated in two stages (i) investigating the association between those PC with first trimester fβhCG and second trimester intact hCG (ihCG), and (ii) studying the association between these two analytes in the same pregnancy. This was a retrospective study in two settings: medical centre that provided data on fβhCG and ihCG levels in pregnancies with FGR and PE, and central laboratory that provided fβhCG and ihCG levels that were compared in the same pregnancy.

The impact of third-trimester genetic counseling.

Objective: To evaluate the impact of genetic counseling (GC) during the third trimester by analyzing changes in pregnancy management and the correlation with postnatal findings.

Methods: This was a retrospective study. Pregnancy course and neonatal follow-up were analyzed according to the reason for referral and implementation of recommendations.

The yield of the prenatal work-up in intrauterine growth restriction and the spectrum of fetal abnormalities detected postnatally .

Objective: To evaluate the yield of work-up in intrauterine growth restriction (IUGR) pregnancies and their outcomes.

Materials And Methods: Retrospective data regarding prenatal work-up (serology, genetic testing and imaging), and neonatal outcomes of 198 IUGR pregnancies (estimated fetal weight <10th percentile) were analyzed.

Results: IUGR was isolated in 72 cases.

When genotype is not predictive of phenotype: implications for genetic counseling based on 21,594 chromosomal microarray analysis examinations.

PurposeTo compare the frequency of copy-number variants (CNVs) of variable penetrance in low-risk and high-risk prenatal samples and postnatal samples.MethodsTwo cohorts were categorized according to chromosomal microarray analysis (CMA) indication: group I, low-risk prenatal-women with uneventful pregnancy (control group); group II, high-risk prenatal-women whose fetuses had congenital malformations; and group III, postnatal-individuals with unexplained developmental delay/intellectual disability, autism spectrum disorders, or multiple congenital anomalies. CNVs were categorized based on clinical penetrance: (i) high (>40%), (ii) moderate (10-40%), and (iii) low (<10%).

The magnitude of elevated maternal serum human chorionic gonadotropin and pregnancy complications.

This study assessed the correlation between the magnitude of the elevation in maternal serum human chorionic gonadotropin (MShCG) levels and pregnancy complications. Among 80,716 screened pregnancies, 120 with moderately elevated MShCG (3.00-5.

Automated image analysis of placental villi and syncytial knots in histological sections.

Introduction: Delayed villous maturation and accelerated villous maturation diagnosed in histologic sections are morphologic manifestations of pathophysiological conditions. The inter-observer agreement among pathologists in assessing these conditions is moderate at best. We investigated whether automated image analysis of placental villi and syncytial knots could improve standardization in diagnosing these conditions.

The mid-gestation triple test profile among women diagnosed with vasa previa.

Purpose: To assess the mid-trimester triple test biomarkers among women diagnosed with vasa previa (VP).

Methods: The study included 43 singleton pregnancies diagnosed with vasa previa between the years 1988 and 2011. The mid-gestation screening test for Down syndrome was calculated from the combination of triple serum markers and maternal age, and expressed as a multiple of the gestation specific normal mean (MoM).

Predictors of twin pregnancy after ovarian stimulation and intrauterine insemination in women with unexplained infertility.

Multi-foetal gestation is a well-known, adverse outcome of infertility treatment. Maternal and obstetrical complications are more frequent in multiple pregnancies compared to singletons. The aim of this study was to determine parameters that affect the risk for multiple pregnancies after ovarian stimulation (OS) with intrauterine insemination (IUI).

Spinocerebellar ataxia type 3 in Israel: phenotype and genotype of a Jew Yemenite subpopulation.

Spinocerebellar ataxia type 3 is an autosomal dominant ataxia with various phenotypes affecting Jews of Yemenite origin in Israel. Clinical and family pedigrees data of 125 Yemenite Jewish patients were collected in our clinic. All examined patients underwent a detailed neurological and bedside vestibular examination.

Telomere homeostasis in placentas from pregnancies with uncontrolled diabetes.

Objective: Diabetes during pregnancy causes an intrauterine environment that influences lifetime sickness of the mother and the fetus. There is a correlation between diabetes and telomere shortening; however, very little is known about telomere homeostasis in the placenta. We aimed to study the telomerase complex in placentas and in cord blood leukocytes from patients with poorly controlled diabetes.

Spectrum of PEX1 and PEX6 variants in Heimler syndrome.

Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities, with or without visual defects. Recently HS was shown to result from hypomorphic mutations in PEX1 or PEX6, both previously implicated in Zellweger Syndrome Spectrum Disorders (ZSSD). ZSSD are a group of conditions consisting of craniofacial and neurological abnormalities, sensory defects and multi-organ dysfunction.

Oocyte activation by calcium ionophore and congenital birth defects: a retrospective cohort study.

Objective: To evaluate the safety of oocyte activation by calcium ionophore in cases of failed fertilization after intracytoplasmic sperm injection (ICSI) procedure with respect to birth defects.

Design: A retrospective cohort of pregnancies achieved by oocyte activation with calcium ionophore after ICSI (ICSI-Ca) and routine ICSI between the years 2006 and 2014.

Setting: Not applicable.

Genomic Alterations Are Enhanced in Placentas from Pregnancies with Fetal Growth Restriction and Preeclampsia: Preliminary Results.

Fetal growth restriction (FGR) secondary to placental insufficiency and preeclampsia (PE) are associated with substantially increased childhood and adult morbidity and mortality. The long-term outcomes are related to placental aberrations and intrauterine programming. Advances in microarray technology allow high-resolution, genome-wide evaluation for DNA copy number variations - deletions and duplications.

Morphometric characteristics of the umbilical cord and vessels in fetal growth restriction and pre-eclampsia.

Background: Reports on the morphometric analysis of umbilical cord (UC) and its vessels have been inconsistent due to varying inclusion criteria and methodology. The current study tried to overcome the limitations of previous studies by comparing the UC in pregnancies complicated by fetal growth restriction (FGR), preeclampsia (PE) and FGR+PE, to healthy controls.

Aims: Analyze the morphometric attributes of the UC in pregnancies complicated by FGR and PE.

Agenesis of the corpus callosum. An autopsy study in fetuses.

Agenesis of the corpus callosum is currently diagnosed prenatally with ultrasound and MRI. While the diagnostic aspects of callosal defects are widely addressed, anatomo-histological data from fetal autopsies are sparse. Callosal defects were present in 50 fetal autopsies.

Is the ratio of maternal serum to amniotic fluid AFP superior to serum levels as a predictor of pregnancy complications?

Purpose: The use of maternal serum alpha fetoprotein (MSAFP) levels as a predictor of pregnancy complications (PC) is well established. We hypothesized that the ratio between the MSAFP/AFAFP levels (RATIO) will more accurately predict PC than MSAFP levels alone.

Methods: Women who had a MSAFP test followed by amniocentesis were divided into two groups: those who had PC comprised the study group and those who had an uneventful pregnancy served as the control group.

Telomere length and telomerase reverse transcriptase mRNA expression in patients with hepatitis C.

Background/aims: Shortened telomeres reflect genetic instability that might lead to increased aneuploidy and malignant transformations. Chronic hepatitis C (HCV) viral infection is considered a pre-neoplastic condition that might progress to hepatocellular carcinoma. We evaluated telomere length and elongation, in patients with different stages of HCV to study the correlation between telomere length and the progression of HCV.

Three peaks in the polymerase chain reaction fragile X analysis.

Objective: To report and discuss the observation of three fragments on polymerase chain reaction (PCR) in routine carrier screening for fragile X.

Methods: From 2005 through 2010, 34,500 women underwent prenatal screening for fragile X. PCR was carried out to amplify the repeat segment.

Increased TERC gene copy number in amniocytes from fetuses with trisomy 18 or a sex chromosome aneuploidy.

Objective: Individuals with chromosomal aneuploidies tend to develop malignancies. Telomerase is an enzyme complex that lengthens telomeres and has enhanced expression in numerous malignancies; one of its components is encoded by the TERC gene. In this study, we evaluated the TERC gene copy number in amniocytes from fetuses with aneuploidy, other than trisomy-21.