Townes-Brocks Syndrome (TBS) is a rare hereditary disorder marked by congenital malformations, posing diagnostic challenges due to its phenotypic heterogeneity. Our nationwide cohort study, encompassing 20,666 individuals with hearing impairment in mainland China, explored the correlation between TBS and variations of SALL1 and DACT1. The study revealed five novel variations in SALL1, alongside two known […]
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Heterozygous deletion of HOXC10-HOXC9 causes lower limb abnormalities in congenital vertical talus
In this communication, we first examine possible associations between the heterozygous deletion of HOXC10-HOXC9 and congenital vertical talus (CVT). CVT, colloquially referred to as “rocket foot”, is a type of foot deformity, with an estimated prevalence of approximately 1 in 10,000 in live births. However, reports on CVT-related genes have been limited. Here, a 18.7-kb […]
Variant Reclassification and Clinical Ramifications
Genetic test results can significantly change the route to diagnosis or the treatment available to a patient with a genetic condition. A DNA change that is detected during diagnostic genetic testing and considered to be associated with a patient’s medical condition is reported to a clinician as a genetic variant. The interpretation of a genetic variant […]
BTB domain mutations perturbing KCTD15 oligomerisation cause a distinctive frontonasal dysplasia syndrome
KCTD15 encodes an oligomeric BTB domain protein reported to inhibit neural crest formation. This study identified de novo missense variants in KCTD15 in two families presenting with a clinically similar, rare phenotype involving frontonasal mass and cutis aplasia or sparse hair. Structural and biophysical analyses demonstrated that these substitutions act through a dominant negative mechanism […]
Expanding the phenotype of Kleefstra syndrome: speech, language, and cognition in 103 individuals
Speech, language, and cognitive impairment are defining features of Kleefstra syndrome but have not been systematically characterised, limiting robust clinical decision making and future planning. We characterised speech, language, and cognition in 103 individuals with Kleefstra syndrome. Language and cognitive ability ranged from average to severely impaired and most verbal individuals had speech production disorders […]
The Mosaic RASopathy concept : different skin lesions, same systemic manifestations?
Epidermal nevi, are mosaic disorders, caused by mutations during embryogenesis, hence affecting only those cells and tissues which had as a precursor this mutated cell. There are many types of epidermal nevi. Variable anomalies in other organs may be associated. In this paper we reviewed syndromic epidermal nevi, caused by mutations in HRAS, KRAS, NRAS […]
Genotype and phenotype correlation of PHACTR1-related neurological disorders
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 […]
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 […]