Our study describes eight individuals with SATB2-associated syndrome (SAS), an autosomal dominant disorder caused by variants in the SATB2 gene and characterized by developmental delay, behavioral challenges, craniofacial/dental problems, growth delay, and skeletal anomalies, all with variable severity. The individuals included carry genetic variants that affect the exact same location in the SATB2 protein but […]
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Rare disease genomic testing in the UK and Ireland: promoting timely and equitable access
Equitable access to timely genomic testing for people affected by rare diseases is required to provide an accurate diagnosis early enough to inform key clinical decisions that modify outcome. This Position Statement describes best practice guidance for the specialist genomics workforce within the national health services in the UK and Ireland. It includes recommendations relating […]
Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults
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. […]
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 […]