Retrotransposons, known as “jumping genes,” move from one location to another across the human genome in a “copy-and-paste” manner and sometimes cause genetic diseases. We used long-read genome sequencing to show that an evolutionarily old SVA_D retrotransposon inserted deep in the intron of ATP7A caused occipital horn syndrome, a rare hereditary copper deficiency. A pedigree analysis indicated […]
Latest articles
Large TRAPPC11 gene deletions as a cause of muscular dystrophy and their estimated genesis
Causative variants in the TRAPPC11 gene are associated with muscular dystrophy and a broad spectrum of other clinical features. We present clinical and molecular genetic findings in three patients who are compound heterozygotes for a missense variant and a multiexon deletion in the TRAPPC11 gene. These are the first structural variants identified in this gene […]
NF2-related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study
Schwannomatosis is a rare tumour predisposition condition. Using a large UK-wide database we have studied the epidemiology of both NF2 and other genetic (LZTR1 and SMARCB1-related) schwannomatoses. We confirm an evenly distributed prevalence of 1 in 58,000 for NF2. A high proportion of cases (72% in England) are de novo (present new in an individual). This is higher than […]
De novo variants in KCNJ3 are associated with early-onset epilepsy
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 […]
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 […]