Genetics of prostate cancer: a review of latest evidence

Prostate cancer is the commonest cancer affecting those born with male reproductive organs and has a strong genetic component. Both common and rare genetic variants are associated with increased prostate cancer risk. It is twice as common in those of African/Afro-Caribbean ancestry. Currently there is no national prostate cancer screening programme due  limitations of screening […]

Read More…

Novel truncating germline variant reinforces TINF2 as a susceptibility gene for familial non-medullary thyroid cancer

It has long been observed that there are families in which thyroid cancer occurs, but no clear causative genes have been found. Some reports showed that shelterin proteins (involved in telomeric regulation) could be related with susceptibility to thyroid cancer. We have found a genetic variant in the TINF2 gene, co-segregating in five affected members […]

Read More…

Is renal cell carcinoma associated with MITF c.952G>A (p.E318K)?

People who have a particular genetic variant in their MITF gene, known as p.E318K, are at increased risk of developing melanoma. The scientific community continues to debate whether this variant also increases the risk of developing renal cell carcinoma (RCC). This manuscript advances this debate by bringing together previous research reports with new research findings. We find that further […]

Read More…

Double gonosomal mosaicism as an unusual hereditary mechanism in familial GRIN2A-related disorder

We studied a family where a mother passed on two different genetic variants at the same nucleotide in the GRIN2A gene to her children. Both variants disrupt the gene function. The son manifest epilepsy and intellectual disability, while the daughter and the mother exhibit language impairment and learning difficulties. The mother carries both variants, with […]

Read More…

Germline testing for breast cancer patients in England: illogical to prioritise grade 1 breast cancer aged 30–39 over grade 3 aged 40–49 years?

Genetic testing for inherited disease-causing changes in breast cancer genes is currently limited by guidelines that determine who is eligible.  Testing breast cancer patients in England was updated in April-2022 making it more widely available, including all women diagnosed under 40years, except those with low grade cancers-(grade-1). However, this exception was recently dropped, apparently to […]

Read More…

IFIH1 variants are associated with generalised epilepsy preceded by febrile seizures

Generalized epilepsy is the most common epilepsy with a prominent genetic etiology. Currently, a substantial number of genes related to generalized epilepsy have not been identified. In this study, we report two de novo heterozygous and three biallelic IFIH1 variants in five unrelated patients with generalized epilepsy with antecedent febrile seizures. Patients showed an early […]

Read More…

Arterial aneurysm and dissection: toward the evolving phenotype of Tatton-Brown-Rahman syndrome

Tatton-Brown Rahman syndrome (TBRS) is a recently described rare disease. The knowledge contributed by new patients is crucial for enhancing our understanding of the condition and, consequently, improving its management and follow-up.  The prevalence of aortic disease in TBRS individuals is far in excess of that expected in the general population. This cohort, together with […]

Read More…

Long-read sequencing identifies an SVA_D retrotransposon insertion deep within the intron of ATP7A as a novel cause of occipital horn syndrome

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 […]

Read More…

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 […]

Read More…

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 […]

Read More…