Distal hereditary motor neuronopathy of the Jerash type (HMNJ) is characterized by distal muscle weakness and atrophy. SIGMAR1 mutations have recently been associated with other motor neuron diseases. We have identified a novel SIGMAR1 c.500A>T missense mutation that is associated with HMNJ in 30 patients. We proved that this mutation reduces the expression and alters […]
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Germline BRCA1 and BRCA2 testing for breast cancer survivors
For patients with early breast cancer knowledge of germline BRCA1/2 status increasingly influences management as well as informing future cancer risk for patients and their families. Newly diagnosed patients are now benefiting from expanded access to testing. To extend this provision to breast cancer survivors, we embedded a Senior Genetic Counsellor in the Breast Unit […]
Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere’s disease
Meniere’s disease (MD) is a rare inner ear disorder with a significant genetic contribution defined by episodic vertigo, sensorineural hearing loss and tinnitus. We performed high-coverage targeted sequencing panel of 263 genes related with the main molecular pathways associated to supporting cells in the inner ear in a large Spanish sporadic MD cohort. We found […]
Homozygous damaging SOD2 variant causes lethal neonatal dilated cardiomyopathy
Cardiomyopathy, or a deterioration of the ability of the heart muscle to contract, generally leads to progressive heart failure. It is frequently inherited, and, because approximately 40% of affected children are likely to die within five years of diagnosis, being able to identify its genetic basis is particularly important. Now, we have identified a new […]
High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers
Constitutional Mismatch Repair Deficiency (CMMRD) is a rare and devastating childhood-onset cancer predisposition syndrome caused by biallelic germline mutations in mismatch repair (MMR) genes. This inherited MMR deficiency causes an accumulation of errors mainly in repetitive regions of the DNA known as microsatellite instability (MSI). We have developed a valuable diagnostic tool that can detect MSI at […]
Open questions on the nature of Parkinson’s disease: from triggers to spreading pathology
Parkinson’s disease (PD) is a late onset neurological condition characterized by impaired movements: tremors, rigidity, slow movements, and abnormal posture. In recent years, numerous non-motor symptoms, including psychiatric, sleep, smell, and digestive alterations, have been identified as integral components of the disease. Loss of smell and constipation can appear a decade before the full motor […]
Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalized therapy: the challenge for the future guidelines
Precision medicin requires the knowledge of constitutive factors of idiosyncratic resilience/vulnerability of a subject to a disease as a prerequisite for a tailored treatment. Phenylketonuria (PKU), a prototypical model of a treatable genetic disorder, has taught us how variable may be the clinical phenotype caused by a monogenic lesion. We are now aware that the […]
Differential disruption of autoinhibition and defect in assembly of cytoskeleton during cell division decide the fate of human DIAPH1-related cytoskeletopathy
Diaphanous-related formins1 (DIA1) is a protein, encoded by DIAPH1 and it assembles the unbranched actin microfilament and microtubule cytoskeleton. As it functions in blood cell as well as hair cell in the cochlea, constitutive activation by the disruption of autoinhibitory interactions between the diaphanous inhibitory domain (DID) and diaphanous auto regulatory domain (DAD) caused by […]
De novo SCAMP5 mutation causes a neurodevelopmental disorder with autistic features and seizures
Our objective was to identify and characterize pathogenic variants in individuals with autistic spectrum disorders (ASD) with developmental delay and seizures. These features are a group of diseases caused by at least 700 different genes. A number of cases remain genetically undiagnosed. We performed exome (protein coding sequences from all genes) sequencing to identify pathogenic […]
New insights into 5α-reductase type 2 deficiency based on a multi-centre study: regional distribution and genotype–phenotype profiling of SRD5A2 in 190 Chinese patients
The 5α-reductase type 2 (5α-RD2) deficiency caused by mutations in the steroid 5α-reductase 2 (SRD5A2) gene results in variable degrees of undervirilization in patients with 46,XY disorders of sex development. Through a multi-center cooperative effort, 190 Chinese subjects diagnosed with 5α-RD2 deficiency were consecutively enrolled, representing the largest case number so far. Based on this, […]