Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC-MS/MS.

In recent years, pathogenic variants in ARS genes, encoding aminoacyl-tRNA synthetases (aaRSs), have been associated with human disease. Patients harbouring pathogenic variants in ARS genes have clinical signs partly unique to certain aaRSs defects, partly overlapping between the different aaRSs defects. Diagnosis relies mostly on genetics and remains challenging, often requiring functional validation of new ARS variants.

A milder form of NSRP1-associated neurodevelopmental disorder, caused by a missense variant in the nuclear localization signal.

Nuclear Speckle Splicing Regulator Protein 1 (NSRP1) is a splice factor found in nuclear speckles, which are small membrane-free organelles implicated in epigenetic regulation, chromatin organization, DNA repair, and RNA modification. Bi-allelic loss-of-function variants in NSRP1 have recently been identified in patients suffering from a severe neurodevelopmental disorder, presenting with neurodevelopmental delay, epilepsy, microcephaly, hypotonia, and spastic cerebral palsy. Described patients acquired neither independent walking nor speech and often showed anomalies on cerebral MRI.

Lethal Capecitabine Toxicity in Patients With Complete Dihydropyrimidine Dehydrogenase Deficiency Due to Ultra-Rare Variants.

A DPD deficiency should be considered in case of severe toxicity even in the absence of common risk variants in DPYD.

Are disease-specific patient-reported outcomes measures (PROMs) used in cardiogenetics? A systematic review.

Patient-reported outcome measures (PROMs) are used to facilitate patient-centered care (PCC). While studies in patients with cardiac conditions have revealed poorer health-related quality of life (HRQoL) and elevated emotional stress, studies in inherited cardiac conditions (ICC) seem rare. A systematic review evaluated which (specific domains of) PROMs are used in patients with ICC.

Comprehensive evaluation of the implementation of episignatures for diagnosis of neurodevelopmental disorders (NDDs).

Episignatures are popular tools for the diagnosis of rare neurodevelopmental disorders. They are commonly based on a set of differentially methylated CpGs used in combination with a support vector machine model. DNA methylation (DNAm) data often include missing values due to changes in data generation technology and batch effects.

Patient-reported outcome measures on mental health and psychosocial factors in patients with Brugada syndrome.

Aims: Brugada syndrome (BrS) is a hereditary arrhythmic disease, associated with sudden cardiac death. To date, little is known about the psychosocial correlates and impacts associated with this disease. The aim of this study was to assess a set of patient-reported psychosocial outcomes, to better profile these patients, and to propose a tailored psychosocial care.

Atrial Abnormalities in Brugada Syndrome: Evaluation With ECG Imaging.

Background: Patients with Brugada syndrome (BrS) have an increased risk of arrhythmias, including atrial tachyarrhythmias (ATas).

Objectives: The purpose of this study was to assess underlying atrial cardiomyopathy in BrS and the effect of ajmaline (AJM) test on the atrium of BrS patients using electrocardiogram imaging (ECGI).

Methods: All consecutive patients diagnosed with BrS in a monocentric registry were screened and included if they met the following criteria: 1) BrS diagnosed following current recommendations; and 2) ECGI map performed before and after AJM with a standard protocol.

Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study.

Background: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype.

Objectives: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes.

Methods: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study.

Searching for a sense of closure: parental experiences of recontacting after a terminated pregnancy for congenital malformations.

Rapid advances in genetic testing have improved the probability of successful genetic diagnosis. For couples who undergo a termination of pregnancy (TOP) due to foetal congenital malformations, these techniques may reveal the underlying cause and satisfy parents' need to know. The aim of this qualitative descriptive research study was to explore couples' experience of being recontacted after a congenital malformation-related TOP, as well as their reasons for participation.

Heart rate variability and microvolt T wave alternans changes during ajmaline test may predict prognosis in Brugada syndrome.

Purpose: Drug-induced type I Brugada syndrome (BrS) is associated with a ventricular arrhythmia (VA) rate of 1 case per 100 person-years. This study aims to evaluate changes in electrocardiographic (ECG) parameters such as microvolt T wave alternans (mTWA) and heart rate variability (HRV) at baseline and during ajmaline testing for BrS diagnosis.

Methods: Consecutive patients diagnosed with BrS during ajmaline testing with 5-year follow-up were included in this study.

Barriers and facilitators for the implementation of patient-centered care in cardiogenetics: a Delphi study among ERN GUARD-heart members.

Current clinical practice regarding inherited cardiac conditions has a biomedical focus, while psychological and social expertize and capacity are often lacking. As patient-centered care entails a multidisciplinary approach, the present study (a) explores barriers and facilitators of implementing patient-centered care in cardiogenetics and (b) contrasts various stakeholder viewpoints and perceived influence. We performed a three-round modified Delphi study using the input of a virtual expert panel comprising 25 medical professionals, 9 psychosocial professionals working in cardiogenetics, and 6 patient representatives.

Identification of differentially methylated regions in rare diseases from a single-patient perspective.

Background: DNA methylation (5-mC) is being widely recognized as an alternative in the detection of sequence variants in the diagnosis of some rare neurodevelopmental and imprinting disorders. Identification of alterations in DNA methylation plays an important role in the diagnosis and understanding of the etiology of those disorders. Canonical pipelines for the detection of differentially methylated regions (DMRs) usually rely on inter-group (e.

SCN5A mutation in Brugada syndrome is associated with substrate severity detected by electrocardiographic imaging and high-density electroanatomic mapping.

Background: Brugada syndrome (BrS) is caused by mutations in SCN5A gene in 15%-20% of cases. Previous studies showed worse prognosis in SCN5A mutation carriers (SCN5A+). To date, there are no data on genotype-phenotype correlation with electrocardiographic (ECG) imaging (ECGI) and high-density epicardial electroanatomic map.

Compound heterozygous null mutations of NOBOX in sisters with delayed puberty and primary amenorrhea.

Background: Premature ovarian insufficiency (POI) is a heterogeneous clinical syndrome defined by a premature loss of ovarian function that associates menstrual disturbances and hypergonatropic hypogonadism. POI is a major cause of female infertility affecting 1% of women before the age of 40 and up to 0.01% before the age of 20.

Novel inactivating follicle-stimulating hormone receptor mutations in a patient with premature ovarian insufficiency identified by next-generation sequencing gene panel analysis.

Objective: To find the genetic etiology of premature ovarian insufficiency (POI) in a patient with primary amenorrhea and hypergonadotropic hypogonadism.

Design: Case report.

Setting: University hospital.

Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial.

Background: Patients with recurrent glioblastoma (rGB) have a poor prognosis with a median overall survival (OS) of 30-39 weeks in prospective clinical trials. Intravenous administration of programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors has low activity in patients with rGB. In this phase I clinical trial, intracerebral (IC) administration of ipilimumab (IPI) and nivolumab (NIVO) in combination with intravenous administration of NIVO was investigated.

Ajmaline Testing and the Brugada Syndrome.

Brugada syndrome (BrS) diagnosis requires the presence of a typical type 1 ECG pattern. Owing to the spontaneous ECG variability, the real BrS prevalence in the general population remains unclear. The aim of the present study was to evaluate the prevalence of positive ajmaline challenge for BrS in a cohort of consecutive patients who underwent electrophysiological evaluation for different clinical reasons.