Christianson syndrome (CS) is an X-linked brain disorder in males characterized by intellectual disability (ID), lack of language, postnatal microcephaly, ataxia, and epilepsy that is caused by mutations in Na+/H+ Exchanger 6 (NHE6). In the largest CS study to-date, we examined 44 CS probands, from 2 to 32 years old, with 31 unique NHE6 variants. […]
Latest articles
The PS4-Likelihood Ratio Calculator: Flexible allocation of evidence weighting for case-control data in variant classification
Observation of a genomic variant at higher frequency in cases with disease compared to population controls can be compelling evidence towards the variant being pathogenic. We present the PS4-Likelihood Ratio Calculator, a tool with which the user defines the odds ratio (representing anticipated underlying strength of disease association for a gene). A likelihood ratio towards […]
Biallelic Variants in α-tubulin Isotypes Cause Female Infertility Characterized as Recurrent Preimplantation Embryo Arrest
The identified genetic basis for Recurrent preimplantation embryo development (RPEA) is limited. This study explored dominant α-tubulin isotypes expressed in oocytes and early embryos and identified biallelic variants in TUBA1C or TUBA4A, resulting in spindle assembly defects and RPEA. The study demonstrates the importance of α-tubulin isotypes in preimplantation embryonic development and highlight novel gene/variant […]
Genetic findings in people with schwannomas who do not meet clinical diagnostic criteria for NF2-related schwannomatosis
NF2-, LZTR1– and SMARCB1-related schwannomatosis share significant clinical overlap. NF2-related schwannomatosis (NF2) is the commonest, but the form of schwannomatosis in people not meeting NF2 criteria is unclear. We summarise genetic findings in paired germline and schwannoma DNA from people with schwannomas, but not meeting NF2 criteria. We show similar proportions of LZTR1, SMARCB1, or mosaic NF2 variants. We also found a […]
Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs)
In this study, Moura et al., analyzed the genomes of two patients with distinct genotypically and phenotypically gastrointestinal stromal tumors (GIST) to identify shared genetic variations that might contribute to tumor development. The authors discovered that both patients had identical deletions in two genes, CFHR1 and CFHR3, which were present in the patient’s normal cells, […]
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 […]
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 […]
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 […]
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 […]
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 […]