Educational tools support informed decision-making for genetic carrier screening in a heterogenic Israeli population.

Reproductive genetic carrier screening (RGCS) aims to provide couples with information to make informed decisions. Since 2013, the Israeli Carrier Screening Program has been offered routinely and free of charge to all Israelis of reproductive age, personalized based on religion, ethnicity, and village/tribe where a disorder is frequent. This study evaluated the impact of two educational tools on an informed choice on RGCS uptake and satisfaction with counselling within a heterogeneous population in northern Israel.

The effect of a prior e-learning tool on genetic counseling outcomes in diverse ethnic couples with abnormal Down syndrome screening tests: A randomized controlled trial.

Genetic counseling (GC) following abnormal Down syndrome (DS) screening tests aims to ensure learning of complex medical concepts and discussion of counselees' personal desires. Pre-GC use of electronic learning tools (e-learning tools) can facilitate GC sessions by allowing more time for dialogue rather than learning medical and genetic concepts, enabling greater focus on the counselee's decisional, psychological, and personal needs. Few studies have investigated such tools for DS screening tests and those who have focused on screening uptake rather than abnormal results and implications.

The landscape of autosomal recessive variants in an isolated community: Implications for population screening for reproductive purposes.

As a result of the preference for consanguineous/endogamous marriages, the Israeli Arab population is composed of isolated communities with relatively frequent autosomal recessive (AR) conditions in each community. Clinical diagnosis of affected individuals has uncovered the pathogenic variants throughout the years. We investigated the diversity of pathogenic AR variants in a single village in northern Israel by exome analysis of 50 random, healthy adults descendants of the founders.

Homozygote loss-of-function variants in the human COCH gene underlie hearing loss.

Since 1999, the COCH gene encoding cochlin, has been linked to the autosomal dominant non-syndromic hearing loss, DFNA9, with or without vestibular abnormalities. The hearing impairment associated with the variants affecting gene function has been attributed to a dominant-negative effect. Mutant cochlin was seen to accumulate intracellularly, with the formation of aggregates both inside and outside the cells, in contrast to the wild-type cochlin that is normally secreted.

Combined loss of LAP1B and LAP1C results in an early onset multisystemic nuclear envelopathy.

Nuclear envelopathies comprise a heterogeneous group of diseases caused by mutations in genes encoding nuclear envelope proteins. Mutations affecting lamina-associated polypeptide 1 (LAP1) result in two discrete phenotypes of muscular dystrophy and progressive dystonia with cerebellar atrophy. We report 7 patients presenting at birth with severe progressive neurological impairment, bilateral cataract, growth retardation and early lethality.

Genetics of hearing loss in the Arab population of Northern Israel.

For multiple generations, much of the Arab population of Northern Israel has lived in communities with consanguineous marriages and large families. These communities have been particularly cooperative and informative for understanding the genetics of recessive traits. We studied the genetics of hearing loss in this population, evaluating 168 families from 46 different villages.

A homozygous TTN gene variant associated with lethal congenital contracture syndrome.

Pathogenic variants in the TTN gene have been reported to cause various cardiomyopathies and a range of skeletal muscle diseases, collectively known as titinopathies. We evaluated a consanguineous family multiple members affected with a lethal congenital contracture syndrome. Using exome sequencing, we identified a homozygous c.

Exploring the genetic basis of 3MC syndrome: Findings in 12 further families.

The 3MC syndromes are a group of rare autosomal recessive disorders where the main clinical features are cleft lip and palate, hypertelorism, highly arched eyebrows, caudal appendage, postnatal growth deficiency, and genitourinary tract anomalies. Ophthalmological abnormalities, most notably anterior chamber defects may also be seen. We describe the clinical and molecular findings in 13 individuals with suspected 3MC syndrome from 12 previously unreported families.

Diagnostic challenges of Wilson's disease presenting as acute pancreatitis, cholangitis, and jaundice.

Wilson's disease is a rare disorder of copper transport in hepatic cells, and may present as cholestatic liver disease; pancreatitis and cholangitis are rarely associated with Wilsons's disease. Moreover, cases of Wilson's disease presenting as pigmented gallstone pancreatitis have not been reported in the literature. In the present report, we describe a case of a 37-year-old man who was admitted with jaundice and abdominal pain.

A novel splice site mutation of CDHR1 in a consanguineous Israeli Christian Arab family segregating autosomal recessive cone-rod dystrophy.

Purpose: To investigate the genetic basis for autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family.

Methods: Patients underwent a detailed ophthalmic examination, including funduscopy, electroretinography (ERG), visual field testing, and optical coherence tomography. Genome-wide homozygosity mapping using a single nucleotide polymorphism array was performed to identify homozygous regions shared between the two affected individuals.

Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1.

Purpose: This study investigated the genetic basis for Usher syndrome type 1 (USH1) in four consanguineous Israeli Arab families.

Methods: Haplotype analysis for all known USH1 loci was performed in each family. In families for which haplotype analysis was inconclusive, we performed genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array.

Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3.

Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive condition, which was defined recently with identification of the causative mutations in G6PC3. To date there are only three reports in the literature describing patients with SCN4 with mutations in the G6PC3 gene. We report four individuals with SCN4 who belong to a single large consanguineous kindred.