Constitutional Mismatch Repair Deficiency Syndrome or CMMRD is a rare, hereditary cancer condition impacting mainly children and young adults. CMMRD individuals get malignant cancers of all types but most commonly brain, intestines (colon) and blood cancers. In the past, most of these patients used to die before adulthood, however, nowadays it is very important to […]
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Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
We inherit 23 chromosomes from each of our parents which contain our DNA and our genes. Some genes can be turn “on” (expressed) or “off” resulting in expression from the maternally or paternally inherited copy, but not both. This process is called Genomic Imprinting. Here we describe a family with a microdeletion within an imprinted […]
Surgical decision making in premenopausal BRCA carriers considering risk-reducing early salpingectomy or salpingo-oophorectomy: a qualitative study
Early removal of tubes followed by later removal of ovaries, offers high-risk women a new two-step option of reducing their ovarian cancer risk, whilst avoiding early menopause. Results from a study in high-risk women undergoing surgical prevention in the UK PROTECTOR trial suggests women more concerned about detrimental impact of menopause chose this new two-step […]
Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers
This is an original research article on uptake, timing and efficacy of bilateral risk reducing surgery (RRM and RRSO) in 887 female BRCA1/BRCA2 carriers unaffected by cancer at testing. This is one of the largest prospective cohorts, covering both surgeries, published to date. More than 50% of women in the study underwent RRM and more […]
Universal germline testing among patients with colorectal cancer: clinical actionability and optimised panel
Our findings provide novel insight into the genetic screening of CRC patients in the era of multi-gene panel. Universal germline testing for cancer susceptibility genes should be recommend among all CRC patients diagnosed under age 70 years. It could discover substantially more individuals with hereditary cancer syndromes who would benefit from enhanced surveillance and tailored […]
Using data from the 100,000 Genomes Project to resolve conflicting interpretations of a recurrent TUBB2A mutation
Variant identification can be challenging for many clinically-relevant genes where highly similar DNA sequences are present elsewhere in the genome. In this study we focused on a recurrent TUBB2A variant (p.A248V) previously described to cause a neurodevelopmental disorder. Due to conflicting assessments in ClinVar and a surprisingly high frequency in some population databases, interpretation of […]
Targeting lung cancer screening to individuals at greatest risk: the role of genetic factors
Lung cancer is the most common global cancer and a leading cause of cancer death. Lung cancer survival is poor, in part due to late diagnosis of the disease. Low-dose CT screening has been shown to reduce lung cancer specific mortality; however, screening must be targeted to those most at-risk to ensure efficiency and reduce […]
DDX58(RIG-I)-related disease is associated with tissue-specific interferon pathway activation
Very few families with mutations in DDX58 (RIG-I), an innate immune sensor, have been described with a multisystem disorder featuring blood vessel calcium deposition, a skin rash, and childhood glaucoma. Here, we have identified two unrelated families that share a rare variant in DDX58, and showed that it causes disease by a gain-of-function mechanism and tissue specific effects. […]
Lyso-Gb3 associates with adverse long-term outcome in patients with Fabry disease
Fabry disease (FD) is a rare X-linked lysosomal storage disease caused by mutations in the α-galactosidase A gene (GLA) leading to enzymatic deficiency of α-galactosidase A and ultimately in progressive glycosphingolipid accumulation, especially globotriaosylceramide (Gb3) and its deacylated derivative globotriaosylsphingosine (Lyso-Gb3). The major metabolite of FD plasma Lyso-Gb3 appears as a potential marker of disease […]
Clinical exome sequencing data reveal high diagnostic yields for congenital diaphragmatic hernia plus (CDH+) and new phenotypic expansions involving CDH
To find new genes that cause congenital diaphragmatic hernia (CDH)—a severe life-threatening birth defect—we used previously published data generated using a machine learning algorithm that compared all genes in the genome to a small set of known CDH genes. By comparing patterns using the machine learning algorithm data, and using information from a clinical database […]