PURA-related neurodevelopmental disorders (PURA-NDDs), encompassing 5q31.3 deletion syndrome and PURA syndrome, are characterized by a constellation of symptoms such as hypotonia, severe global developmental delay, and seizures. This systematic review demonstrates that the clinical severity of PURA-NDDs is primarily associated with the extent of PUR-repeat disruption rather than the specific variant location. Notably, PURA variants […]
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Advances in research on the mechanism of tsRNA action in tumours (Contributed by Professor Ming Lei)
At present, many studies have emphasized the importance of tsRNAs in tumors and revealed their important role in the biological processes of tumor cell proliferation, apoptosis, and metastasis. By systematically analyzing the production and biological function of tsRNAs in various tumors, we elucidate its mechanism of action in tumor occurrence and progression, and discuss their […]
A founder deletion involving BRCA1 in families of Nepalese origin: the perfect hiding place! (Contributed by Dr. Alistair T Pagnamenta)
Deletions and duplications involving the BRCA1 gene can be found in a substantial proportion of families with inherited risk for breast and ovarian cancer. In this study, Pagnamenta et al identified two affected cousins from the 100,000 Genomes Project who shared a complex 178bp deletion in BRCA1. Due to its size and location, the deletion had escaped detection using multiple […]
Retrospective study on the utility of optical genome mapping as a follow-up method in genetic diagnostics (Contributed by Dr. Paul Dremsek)
Genetic tests currently used in routine diagnostics are designed to detect almost all types of genetic aberrations that may cause disease. However, in some cases, aberrations can be detected, but remain partly unresolved: e.g., the detection of a large duplication often does not entail information on its point of insertion in the genome, which could […]
Aortic and Arterial Manifestations and Clinical Features in TGFB3-Related Heritable Thoracic Aortic Disease: Results from the Montalcino Aortic Consortium (Contributed by Dr. Michelle Su-Anne Lim)
This paper describes clinical features and aortic outcomes in patients with heritable thoracic aortic disease (HTAD) due to TGFB3 variants. Aortic dilation occurred in some but not all individuals, but aortic dissection (a tear in the aortic wall) occurred in very few patients and at older ages and at larger aortic diameters than in those […]
Unveiling non-coding DMD variants: synergising RNA sequencing and DNA sequencing for enhanced molecular diagnosis (Contributed by Dr. Yinghong Pan)
By combining RNA sequencing with DNA analysis and immunohistochemistry , this study uncovered hidden pathogenic variants that traditional methods often miss for Duchenne and Becker muscular dystrophy (DMD/BMD) testing. Pan et al. identified splice-altering variants and complex DNA rearrangements in patients with unresolved DMD molecular diagnoses, enabling more precise detection of disease-causing changes. This innovative […]
Novel HYLS1 variants associated with Joubert syndrome suggest potential genotype-phenotype correlates (Contributed by Dr. Fulvio D’Abrusco)
Joubert syndrome (JS) is a rare genetic ciliopathy, whose diagnostic hallmark is the “molar tooth sign” on brain MRI. Mutations in over 40 different genes can cause JS, many of which are involved in the proper functioning of primary cilia. HYLS1 gene is associated with a severe condition called Hydrolethalus syndrome, leading to early death. […]
Novel germline TP53 variant (p.(Phe109Ile)) confers high risk of cancer (Contributed by Dr. Anna Byrjalsen)
This paper concerns five patients who carry a novel genetic variant in a gene (TP53) that cause a high risk of childhood cancer. Three of the children developed cancer before age 18, two children have had two successive cancers. All five children were conceived by the help of a sperm donor. The aim with this […]
From onset to blindness: a comprehensive analysis of RPGR-associated X-linked retinopathy in a large cohort in China (Contributed by Jiawen Wu and Jihong Wu)
Mutations in the RPGR gene are the most common cause of X-linked retinopathy, a hereditary retinal disease. We have thoroughly characterized the clinical features and natural history of a large cohort of patients with RPGR-associated X-linked retinopathy, documenting the progression from onset to blindness. This detailed analysis provides valuable insights into the disease’s timeline, offering […]
Estimating cancer risk in carriers of Lynch syndrome variants in UK Biobank (Contributed by Eilidh Fummey)
Lynch syndrome (LS) is a genetic condition that increases risk of some cancers. Typically, cancer risk in LS is estimated using individuals with an individual or family history of cancer. This may upwardly bias estimates. We estimated cancer risk in LS using a population-based cohort not selected on history of cancer. These estimates were generally […]