PHACTR1(phosphatase and actin regulators) plays a key role in cortical migration and synaptic activity by binding and regulating G-actin and PPP1CA. Patients with variants in PHACTR1 can have a phenotype of developmental encephalopathy in addition to infantile epileptic spasms syndrome (IESS). Using AlphaFold-Multimer, our findings indicate that PHACTR1 and G-actin binding sequences overlap with PPP1CA […]
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GRN mutation spectrum and genotype–phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort
Heterozygous mutations in the GRN, especially of the loss of function type, are causative of Frontotemporal dementia (FTD). However, several GRN variants can be found in other neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease. We reported 14 Chinese subjects with the rare variants of GRN (NM_002087.3). They presented with behavioral variant of […]
Clinical implications of VUS reclassification in a single-center series from application of ACMG/AMP classification rules specified for BRCA1/2
The detection of variants of uncertain significance (VUSs) in BRCA1/2 genes poses challenges in counseling and managing cancer patients. In this work, we have reviewed all BRCA1/2 VUSs detected in our clinical service in Bologna (Italy) over the past 11 years following recently developed classification guidelines, yielding a classification rate of 81.3%. This result demonstrates […]
Breast cancer risk in NF1-deleted patients
Neurofibromatosis type 1 (NF1) is a genetic condition characterized by increased risk of developing tumors, as well as various other physical and neurological manifestations. NF1 women were previously reported to have an increased risk of breast cancer. There are different genetic variants causing NF1: in ~5-10% of patients, large deletions of the entire NF1 locus […]
Recontact to return new or updated PALB2 genetic results in the clinical laboratory setting
Duty to re-contact patients for updated genetic test results is a widely discussed topic and is routinely practiced by clinical laboratories. However, publications documenting results from retrospective testing are lacking. Within a cohort of 2977 individuals with Hereditary Breast and Ovarian Cancer and previously negative or inconclusive BRCA1/BRCA2 results, reanalysis found a new pathogenic variant […]
Germline testing of BRCA1, BRCA2, PALB2 and CHEK2 c.1100delC in 1514 triple negative familial and isolated breast cancers from a single centre, with extended testing of ATM, RAD51C and RAD51D in over 400
Alterations of certain genes may place women at increased risk of developing a subtype of breast cancer not expressing hormone receptors, triple negative breast cancer (TNBC). We undertook a review of the gene alterations seen in women in Manchester with TNBC and showed there is an increased risk of developing TNBC where there is an […]
Reduced penetrance of gene variants causing amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are incurable neurodegenerative diseases with shared pathology and genetics . We know how common ALS and FTD are, how often they run in families and how often specific genes are implicated. We used published literature and population-level data about genomic variation to calculate how common disease-causing variants […]
Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia
Classical aniridia is an eye malformation caused by the loss of one working copy of the PAX6 gene, but a minority of cases remain genetically unsolved. We sequenced the whole genomes of 37 affected families (51 individuals) where PAX6 had previously been sequenced but no causative mutation was found. We found a genetic cause in 22 (60%) families. 19 cases had […]
Ancestry, race and ethnicity: the role and relevance of language in clinical genetics practice
Clinicians are often asked to document a patient’s ethnicity when requesting certain types of medical investigations. For example, the genomic medicine service in England wants this information to help guide the interpretation of certain genetic findings. In the US, a patient’s race might be similarly documented. However, the terms ethnicity, or race, or indeed ancestry, […]
Clinical and genetic spectrum of RNF216-related disorder: A new case and literature review
RNF216-related disorder is a rare neuroendocrine disease resulting from RNF216 gene mutations with diverse symptoms and inheritance pattern. This study reported a new case with a novel causative RNF216 variant and reviewed all individuals with causative RNF216 variants in previous reports. We found that ataxia was the most frequent initial symptoms in individuals under 30 […]