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. […]
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Novel germline TP53 variant (p.(Phe109Ile)) confers high risk of cancer
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
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
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 […]
Robust detection of pathogenic HYDIN variants that cause primary ciliary dyskinesia using RNA-seq of nasal mucosa
Primary ciliary dyskinesia (PCD) is a rare inherited condition that makes it hard for the body to clear germs from the lungs and nose, causing frequent infections. It is often confused with other illnesses, so genetic testing is important for a correct diagnosis. One tricky gene involved is HYDIN, as it has a nearly identical […]
Li-Fraumeni Syndrome: a germline TP53 splice variant reveals a novel physiological alternative transcript
This study addresses a genetic mutation linked to Li-Fraumeni syndrome (LFS), a condition that heightens the risk of multiple early cancers. The mutation, located in the TP53 gene, disrupts its normal function. Initially considered uncertain, this novel variant was later redefined as “pathogenic” after demonstrating reduced activity of the p53 protein, which protects cells from […]
Cystic fibrosis carrier screening in Australia: comparing sequencing and targeted panels across diverse ancestries
Screening for cystic fibrosis (CF) is common in Western countries before pregnancy to assess the risk of having a child with CF. Most tests focus only on common mutations. This study shows that these targeted approaches are less effective for people of non-European ancestry, particularly those of South Asian descent. It also reveals that some […]
Congenital urinary tract anomalies are a variable finding associated with nevoid basal cell carcinoma syndrome
Nevoid basal cell carcinoma syndrome (NBCCS) is a genetic disorder known for causing skin cancers and jaw cysts, but it has a wide breadth of additional manifestations across multiple organ systems, which may go unrecognized. This study explores the link between NBCCS and urinary tract anomalies by examining affected patients at a single center, where […]
Validation of the NCCN/Yale criteria for the identification of CDH1 pathogenic variant carriers
Individuals carrying mutations in the CDH1 gene are at increased risk of developing stomach cancer (lifetime risk 7-42%) and breast cancer (lifetime risk 37-55%). Identification of these individuals through genetic testing is important because these cancers can be prevented by prophylactic surgery or detected early with endoscopy and breast imaging. Guidelines recommend genetic testing when […]
Foecal incontinence disorders in Wolfram syndrome: a new manifestation
Wolfram syndrome type 1 is an autosomal recessive neurodegenerative disease causing many symptoms: insulin-dependent diabetes, optic neuropathy, hearing loss, diabetes insipidus, urinary disorders and balance disorders. A patient association alerted us to the possible existence of fecal incontinence in this syndrome. To confirm its existence of this symptom in this disease, we sent a questionnaire […]