Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome.

Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WW domain-binding protein 4 (WBP4) is part of the early spliceosomal complex and has not been previously associated with human pathologies in the Online Mendelian Inheritance in Man (OMIM) database. Through GeneMatcher, we identified ten individuals from eight families with a severe neurodevelopmental syndrome featuring variable manifestations.

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.

Information Women Choose to Receive About Prenatal Chromosomal Microarray Analysis.

Objective: To examine the choices of women with both high-risk and low-risk pregnancies who are undergoing prenatal chromosomal microarray analysis in a clinical setting regarding three challenging types of findings: variants of uncertain clinical significance, susceptibility loci for neurodevelopmental disorders, and copy number variants associated with risks for adult-onset conditions. We assessed whether women's choices were associated with indications for testing or with one-on-one pretest genetic counseling.

Methods: In this cross-sectional study, medical records of women who underwent invasive prenatal chromosomal microarray analysis testing (N=1,070) at Hadassah Medical Center between June 2017 and February 2018 were examined for testing indications, choices regarding chromosomal microarray analysis findings, and type of pretest genetic counseling.

Recurrent TP53 missense mutation in cancer patients of Arab descent.

Hereditary cancer comprises more than 10% of all breast cancer cases. Identification of germinal mutations enables the initiation of a preventive program that can include early detection or preventive treatment and may also have a major impact on cancer therapy. Several recurrent mutations were identified in the BRCA1/2 genes in Jewish populations however, in other ethnic groups in Israel, no recurrent mutations were identified to date.

The outcome of pregnancy following topiramate treatment: a study on 52 pregnancies.

In spite of a substantial increase in the use of topiramate at child bearing age, very little is known regarding its use in pregnancy. We describe the outcome of 52 pregnancies with 41 liveborn infants from which it seems that topiramate reduces birth weight without decreasing gestational age at delivery, but does not seem to increase the risk for structural defects. There was an increased rate of spontaneous abortions not related to the drug effects.