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 […]
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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 […]
Biallelic variants in Plexin B2 (PLXNB2) cause amelogenesis imperfecta, hearing loss and intellectual disability
Plexins are receptors for Semaphorin signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical during development and in adult life stages. We identified biallelic variants in Plexin B2 (PLXNB2) through exome or genome sequencing in eight people from six families, each of whom have a syndromic condition including amelogenesis imperfecta and hearing loss. Intellectual […]
Survey of service needs to embed genome sequencing for motor neuron disease in neurology in the English National Health Service
Everyone with MND in England is now eligible for a test to see if their MND is linked to their genes, i.e. genome sequencing. We surveyed 245 neurology and genetics clinicians about their genetic knowledge, experience and training. Neurology clinicians reported multiple barriers to offering genome sequencing. Further, they rated their confidence in genetics knowledge […]
Dissecting Genetic Architecture of Rare Dystonia: Genetic, Molecular and Clinical Insights
Dystonia is one of the most common movement disorders. This is the first study that covers dystonia families from Turkey, the population of which is known to be a mixture of populations from the Middle East, the Caucasus, the Balkans, Central Asia, and Europe. We identified potentially disease-causing variants in the established dystonia genes (PRKRA, […]
Bi-allelic variants in chromatoid body protein TDRD6 cause spermiogenesis defects and severe oligoasthenoteratozoospermia in humans
TDRD6 (Tudor domain-containing 6), plays a crucial role in spermiogenesis and male infertility by maintaining the structural integrity of chromatoid bodies (CBs) and regulating post-meiotic gene expression in mice. However, the association between the TDRD6 variants and human infertility remains unclear due to limited sample size. We reported bi-allelic TDRD6 variants in five unrelated Chinese […]
Molecular Diagnosis, Clinical Evaluation, and Phenotypic Spectrum of Townes-Brocks Syndrome: Insights from a large Chinese hearing loss Cohort
Townes-Brocks Syndrome (TBS) is a rare hereditary disorder marked by congenital malformations, posing diagnostic challenges due to its phenotypic heterogeneity. Our nationwide cohort study, encompassing 20,666 individuals with hearing impairment in mainland China, explored the correlation between TBS and variations of SALL1 and DACT1. The study revealed five novel variations in SALL1, alongside two known […]