"I'm quite proud of how we've handled it": health professionals' experiences of returning additional findings from the 100,000 genomes project.

Participants in the 100,000 Genomes Project (100kGP) could consent to receive additional finding (AF) results, individual variants relating to genes associated with susceptibility to cancer and familial hypercholesterolemia (FH). In the study reported here, qualitative interviews were used to explore the experiences of National Health Service (NHS) professionals from across England who were tasked with returning over 80,000 "no AF" results and 700 positive AF results to 100kGP participants. Interviews were conducted with 45 professionals from a range of backgrounds, including Genetic Counsellors, Clinical Geneticists, FH Clinical Nurse Specialists and Clinical Scientists.

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.

Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome.

The shift to a genotype-first approach in genetic diagnostics has revolutionized our understanding of neurodevelopmental disorders, expanding both their molecular and phenotypic spectra. Kleefstra syndrome (KLEFS1) is caused by EHMT1 haploinsufficiency and exhibits broad clinical manifestations. EHMT1 encodes euchromatic histone methyltransferase-1-a pivotal component of the epigenetic machinery.

The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers.

Objectives: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2).

Subjects And Methods: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years.

Clinical and molecular characterization of patients with YWHAG-related epilepsy.

Objective: YWHAG variant alleles have been associated with a rare disease trait whose clinical synopsis includes an early onset epileptic encephalopathy with predominantly myoclonic seizures, developmental delay/intellectual disability, and facial dysmorphisms. Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG-related epilepsy.

Methods: We included in this study 24 patients, 21 new and three previously described, with pathogenic/likely pathogenic variants in YWHAG.

Survey of service needs to embed genome sequencing for motor neuron disease in neurology in the English National Health Service.

All people with motor neuron disease (pwMND) in England are eligible for genome sequencing (GS), with panel-based testing. With the advent of genetically targeted MND treatments, and increasing demand for GS, it is important that clinicians have the knowledge and skills to support pwMND in making informed decisions around GS. We undertook an online survey of clinical genomic knowledge and genetic counselling skills in English clinicians who see pwMND.

ASXL3-related disorder: Molecular phenotyping and comprehensive review providing insights into disease mechanism.

ASXL3-related disorder, sometimes referred to as Bainbridge-Ropers syndrome, was first identified as a distinct neurodevelopmental disorder by Bainbridge et al. in 2013. Since then, there have been a number of case series and single case reports published worldwide.

A report of resources used by clinicians in the UK to support motor neuron disease genomic testing.

Genetic testing is a key decision-making point for people with motor neuron disease (MND); to establish eligibility for clinical trials, better understand the cause of their condition, and confirm the potential risk to relatives, who may be able to access predictive testing. Given the wide-reaching implications of MND genetic and predictive testing, it is essential that families are given adequate information, and that staff are provided with appropriate training. In this report we overview the information resources available to people with MND and family members around genetic testing, and the educational and training resources available to staff, based on information obtained through a freedom of information request to UK-based NHS Trusts.