An estimated 3% of endometrial cancers are caused by Lynch Syndrome. These can be identified via a step-wise testing pathway of somatic tumour testing followed by germline gene testing. Using complete national data amalgamated from diagnostic laboratories via the English National Disease Registration Service, we conducted a retrospective national population-based observational study of Lynch Syndrome testing in […]
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Commentary on Estimating cancer risk in carriers of Lynch syndrome variants in UK Biobank
Lynch syndrome is now considered to comprise four different heritable conditions, each caused by changes in a different gene and resulting in different levels of cancer risk. We previously calculated and published these risks according to age and sex, using the Prospective Lynch Syndrome Database. We also showed that colonoscopy does not prevent bowel cancer […]
UBTF haploinsufficiency associated with UBTF-related global developmental delay and distinctive facial features without neuroregression
The UBTF gene produces two important proteins, UBTF1 and UBTF2. A specific change in the UBTF gene, called a gain-of-function mutation, has been linked to a condition called CONDBA. However, until now, there haven’t been any reports of patients with a different kind of issue—having only one working copy of the UBTF gene (this is […]
Canadian College of Medical Geneticists: clinical practice advisory document – responsibility to recontact for reinterpretation of clinical genetic testing
There are currently differences and a lack of guidance for what to do about recontacting former patients when there may be changes in clinical genetics result interpretation. While there is no duty by law to do it, there may be a shared responsibility between the laboratory practitioners, ordering clinicians and the patient. This document discusses […]
Pathogenic SATB2 missense variants affecting p.Gly392 have variable functional implications and result in diverse clinical phenotypes
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 […]
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 […]