Epilepsy is a common chronic neurological disorder characterized by recurring spontaneous seizures with cognitive and psychosocial comorbidities. Genetic factors play a crucial role in the cause of epilepsy. We report two patients with epilepsy carrying the variants in KCNJ3 gene, which encodes a potassium channel. For the patients, the seizures occurred at a young age […]
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Novel TFG mutation causes autosomal-dominant spastic paraplegia and defects in autophagy
Mutations in the tropomyosin receptor kinase fused (TFG) have been identified as contributing to several neurological disorders: hereditary spastic paraplegia (HSP), hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P), and Charcot-Marie-Tooth disease type 2 (CMT2). Here, we describe a novel heterozygous TFG variant (p.R42Q) responsible for pure HSP. We have further confirmed that […]
Intellectual disability syndrome associated with a homozygous founder variant in SGSM3 in Ashkenazi Jews
Neurodevelopmental disorders (NDDs) affect brain development and function, with varying symptoms and genetic causes. While some RAS superfamily proteins are known to contribute to NDDs, the role of SGSM (small G protein signaling modulator) remained unexplored. A recent study changed that, identifying an SGSM3 gene founder variant in 13 patients from 8 Ashkenazi Jewish families. […]
Functional annotation with expression validation identifies novel metastasis-relevant genes from post-GWAS risk loci in sporadic colorectal carcinomas
Metastasis to distal organ is the major cause of cancer death. The underlying germline genetic factors for colorectal cancer (CRC) metastasis are currently unclear. This study identifies metastasis-relevant genes and pathways via a combinatorial strategy of genome-wide association study (GWAS) of clinically defined 1282 metastasis-positive vs 1395 metastasis-negative cases, in silico functional annotation and pathway […]
Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS): new insights from the fetal perspective
Tonne-Kalscheuer syndrome (TOKAS) is a rare disorder with intellectual disability and multiple congenital abnormalities. TOKAS is caused by pathogenic variants in the RLIM gene located on the X-chromosome. Men are affected, while carrier women are usually asymptomatic. Of the 41 patients reported with TOKAS, only 7 antenatal cases were described. We present here 11 antenatal […]
Validation of the BOADICEA model in a prospective cohort of BRCA1/2 pathogenic variant carriers
BOADICEA is a multifactorial breast cancer risk model for predicting the future breast cancer risk based on the joint effects of cancer family history, lifestyle, hormonal and reproductive risk factors, polygenic risk score and rare pathogenic variants. Here, Yang et al validated for the first time the full multifactorial model in 1,614 BRCA1 and 1,365 […]
Encephalocraniocutaneous lipomatosis phenotype associated with mosaic biallelic pathogenic variants in the NF1 gene
This paper explores a rare congenital condition called encephalocraniocutaneous lipomatosis (ECCL), which affects the eyes, skin and brain. Researchers examined a patient with neurofibromatosis type 1 (NF1), a genetic disorder, who also exhibited the typical features of ECCL. Genetic analysis of brain and other tissues revealed a distinct mosaic pattern of alterations in the NF1 […]
ZFYVE19 deficiency: a ciliopathy involving failure of cell division, with cell death
ZFYVE19 deficiency is known as a unique ciliopathy that only involves liver, presenting as neonatal cholestasis, progressive portal fibrosis and portal hypertension. In this paper, we demonstrated that Zfyve19 knockout mice when unchallenged showed no obvious abnormalities but recapitulated postnatal aspects of ZFYVE19-deficient patient upon exposure to a biliary insult, prompting that ZFYVE19 deficiency might […]
Variant classification changes over time in the clinical molecular diagnostic laboratory setting
Appropriately classifying genetic testing results is necessary for patients to receive proper care. As more information is discovered about certain genes and their variants/mutations, prior classifications can be updated accordingly. We aimed to study the reclassifications of genetic variants from patients seen at hereditary cancer clinics in Ontario. Of the variants included in this study, […]
An expanded targeted preconception screening panel in Israel – findings and insights
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 […]