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 […]
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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 […]
Heterozygous deletion of HOXC10-HOXC9 causes lower limb abnormalities in congenital vertical talus
In this communication, we first examine possible associations between the heterozygous deletion of HOXC10-HOXC9 and congenital vertical talus (CVT). CVT, colloquially referred to as “rocket foot”, is a type of foot deformity, with an estimated prevalence of approximately 1 in 10,000 in live births. However, reports on CVT-related genes have been limited. Here, a 18.7-kb […]
Variant Reclassification and Clinical Ramifications
Genetic test results can significantly change the route to diagnosis or the treatment available to a patient with a genetic condition. A DNA change that is detected during diagnostic genetic testing and considered to be associated with a patient’s medical condition is reported to a clinician as a genetic variant. The interpretation of a genetic variant […]
BTB domain mutations perturbing KCTD15 oligomerisation cause a distinctive frontonasal dysplasia syndrome
KCTD15 encodes an oligomeric BTB domain protein reported to inhibit neural crest formation. This study identified de novo missense variants in KCTD15 in two families presenting with a clinically similar, rare phenotype involving frontonasal mass and cutis aplasia or sparse hair. Structural and biophysical analyses demonstrated that these substitutions act through a dominant negative mechanism […]