We present the results of an Israeli expanded carrier screening panel (IL-ECSP) in a cohort of 10,115 Israeli participants. The IL-ECSP is a curated variant-based targeted preconception screening test, tailored to the diverse Israeli population, including its minorities. Utilizing this panel, we identified 2.6% at-risk couples, almost twice higher than those that would have been […]
Latest articles
Comprehensive genomic filtering algorithm to expose the cause of skewed X chromosome inactivation. The proof of concept in female haemophilia expression
Inherited disorders linked to the X-chromosome, like haemophilia, commonly affect men, whilst carrier women are typically unaffected. X-chromosome inactivation (XCI) is a normal process in women that compensates X-doses with men, where each woman cell silences either the paternal, or maternal X, in similar proportion. Certain genetic factors skewed-XCI generating female cells preferentially silencing only […]
Genetic evidence for splicing-dependent structural and functional plasticity in CASK protein
Mutations in the gene CASK disrupt brain growth and cause global developmental delay, with the hindbrain (including the cerebellum) disproportionately affected. Here we show that the cerebellum, but not forebrain, remains vulnerable to CASK loss throughout life, and surprisingly, certain CASK mutations affect the forebrain without cerebellar involvement. These mutations disrupt a CASK protein conformation that is specific to vertebrates and likely to have distinct molecular function/s. Based on this evidence, we propose that […]
Novel mutation leading to splice donor loss in a conserved site of DMD gene causes Duchenne muscular dystrophy with cryptorchidism
In a landmark study, our team has unveiled crucial insights into cryptorchidism, a prevalent male birth defect where testicles do not descend properly. By examining the genetic blueprint of affected individuals, we identified new and known genes linked to this condition, primarily on the X chromosome, suggesting a pattern of inheritance from the mother. This […]
Pathogenic variant detection rate varies considerably in Male breast cancer families and sporadic cases: minimal additional contribution beyond BRCA2, BRCA1 and CHEK2
Male breast cancer (MBC) affects around 1 in 1000 men and is known to have a higher underlying cause from high and moderate risk gene pathogenic variants (PV) than female breast cancer, particularly in BRCA2. However, most studies only report overall detection rates without assessing detailed family history. We reviewed genetic testing in 204 families […]
BRCA awareness and testing experience in the UK Jewish population: a qualitative study
Jewish people have a higher risk of carrying an alteration in the BRCA genes, which cause breast and ovarian cancer. This is the first UK study to explore Jewish peoples’ experiences of genetic-testing. We interviewed 32 people, and found that nobody regretted having testing, although there was huge variation in satisfaction. Many people had issues […]
Phenotypic characterisation of SMAD4 variant carriers
In this observational study, we describe the phenotype of 33 patients carrying SMAD4 variants. Both hereditary haemorrhagic telangiectasia (HHT), a rare vascular genetic disease, and juvenile polyposis syndrome (JPS), a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers, are known to be caused by SMAD4 pathogenic variants. Given SMAD4’s crucial role […]
Subcellular localisation of truncated MAGEL2 proteins: insight into the molecular pathology of Schaaf-Yang syndrome
Our research focuses on Schaaf-Yang syndrome (SYS), an ultra rare neurodevelopmental disease caused by truncating mutations in the MAGEL2 gene. Particularly, in this study we explore how these mutations affect the localization of the MAGEL2 protein within cells. By heterologous expression of tagged proteins we found that the truncated forms tend to accumulate more in […]
A comparative medical genomics approach may facilitate the interpretation of rare missense variation
This study compares rare genetic variation in humans and in nine domestic animal species. We found that variants causing disease in these non-human animals tend to also cause disease in humans. The findings suggest that data from DNA sequencing in veterinary medicine could aid in interpreting rare genetic variation seen in the clinic. Our results […]
ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favorable outcomes
Epilepsy is a common neurological disorder with age-dependent seizures, which includes developmental and epileptic encephalopathy (DEE), a severe form of epilepsy. This study identified ZFHX3 as a pathogenic gene of DEE and partial epilepsy. All patients with ZFHX3 variants achieved seizure-free after appropriate treatment. Studies in fly, mouse, and human all showed that ZFHX3 is highly expressed in the embryonic stage and decreased dramatically […]