Amyotropic lateral sclerosis (ALS) is the commonest form of motor neuron disease, with some cases caused by mutations in the C9ORF72 gene. At our tertiary neurosciences clinic, we compared a group of ALS patients with the C9ORF72 mutation to a group without the mutation. Patients with the C9ORF72 mutation were more likely to present with […]
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Variants in the gene DNA2 causes Rothmund-Thomson syndrome-like presentation
Rothmund-Thomson syndrome is a rare genetic disorder caused by variants in both copies of ANAPC1 or RECQL4 genes. We report on six Brazilian individuals and two siblings of Swiss/Portuguese ancestry who presented severe short stature, poikiloderma and congenital ocular anomalies. Genomic analysis revealed that all patients harbored variants in both copies of DNA2, one variant, […]
Early breast cancer risk detection: a novel framework leveraging polygenic risk scores and machine learning
Despite great progress in the identifications of genes associated with breast cancer, there is still limited use of such knowledge in breast cancer (BC) screening, with nearly one-third of BC patients still missing the early detection phase. We have developed BRECARDA, an AI-based framework that incorporates genetic information and clinical risk factors to predict breast […]
Strategic validation of variants of uncertain significance in ECHS1 genetic testing
Nowadays, genetic testing can provide an accurate diagnosis for hereditary disorders in general practice. Currently, the accumulation of variants of unknown significance (VUSs) during genetic testing is a major problem and rate-limiting step in genetic diagnosis. This study provides a novel and high-throughput methodology to solve this problem and promotes rapid evaluations of VUSs. Further […]
Germline (epi)genetics reveals high predisposition in females: a 5-year, nationwide, prospective Wilms tumour cohort
Wilms tumors, a rare form of kidney cancer that typically affects children, can be caused by high-penetrance genetic or epigenetic factors. However, studies systematically examining both these aspects of the disease are scarce. In a new study, researchers offered germline whole-genome sequencing to all participants diagnosed with Wilms tumors from 2016 to 2021 in Denmark. […]
Validation and depth evaluation of low-pass genome sequencing in prenatal diagnosis using 387 amniotic fluid samples
Low-pass genome sequencing (LP GS) has been widely used in CNV detection andis considered as an alternative to chromosomal microarray analysis. However, application of LP GS as a first-line prenatal diagnostic test is not ready.The increase in sequencing depth will improve detection sensitivity, followed by the increase for cost. This could greatly block the successful […]
The crucial role of titin in fetal development: recurrent miscarriages and bone, heart and muscle anomalies characterise the severe end of titinopathies spectrum
TTN gene encodes for titin, the largest protein in the human body, with a crucial role in the development and functioning of the sarcomere. Here, we collected clinical and molecular data from a cohort of early-onset recessive titinopathy cases, and we proved that biallelic titin pathogenic variants cause recognizable fetal and developmental defects. Also, we […]
PSMD3 gene mutations cause pathological myopia
Pathological myopia (PM) is one of the major causes of irreversible blindness worldwide. However, its exact genetic and pathogenic mechanism remains unclear. This study identifies a novel gene, PSMD3 (proteasome 26S Subunit, Non-ATPase3), with a missense mutation in a PM family. Mutation of PSMD3 decreases the mRNA and protein expression, causing apoptosis of human retinal […]
MSH2 is the very young onset ovarian cancer predisposition gene, not BRCA1
The genetic cause in women diagnosed with ovarian cancer (OC) under thirty years of age is unclear. It is known that the histology and genetics of these cancers are different to those in the general OC patient population. On reviewing the genes affected in women diagnosed under thirty years in the North-West of England we […]
Update of penetrance estimates in Birt-Hogg-Dubé syndrome
Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disorder associated with lung cysts, collapsed lungs, skin lesions, and an increased risk of both benign and malignant renal tumours. In addition to the accepted phenotypic presentation of BHD, it has been suggested that colonic polyps may also be associated with BHD syndrome. This analysis provides more precise […]