Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis.

While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review.

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.

Diagnostic and prognostic relevance of using large gene panels in the genetic testing of patients with dilated cardiomyopathy.

It was previously suggested that increasing the number of genes on diagnostic gene panels could increase the genetic yield in patient with dilated cardiomyopathy (DCM). We explored the diagnostic and prognostic relevance of testing DCM patients with an expanded gene panel. The current study included 225 consecutive DCM patients who had no genetic diagnosis after a 48-gene cardiomyopathy-panel.

Prevalence and Clinical Consequences of Multiple Pathogenic Variants in Dilated Cardiomyopathy.

Background: Dilated cardiomyopathy (DCM) was considered a monogenetic disease that can be caused by over 60 genes. Evidence suggests that the combination of multiple pathogenic variants leads to greater disease severity and earlier onset. So far, not much is known about the prevalence and disease course of multiple pathogenic variants in patients with DCM.

Prevalence of intronic repeat expansions in RFC1 in Dutch patients with CANVAS and adult-onset ataxia.

Recently, an intronic biallelic (AAGGG) repeat expansion in RFC1 was shown to be a cause of CANVAS and adult-onset ataxia in multiple populations. As the prevalence of the RFC1 repeat expansion in Dutch cases was unknown, we retrospectively tested 9 putative CANVAS cases and two independent cohorts (A and B) of 395 and 222 adult-onset ataxia cases, respectively, using the previously published protocol and, for the first time optical genome mapping to determine the size of the expanded RFC1 repeat. We identified the biallelic (AAGGG) repeat expansion in 5/9 (55%) putative CANVAS patients and in 10/617 (1.

Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy.

Purpose: Accurate interpretation of variants detected in dilated cardiomyopathy (DCM) is crucial for patient care but has proven challenging. We applied a set of proposed refined American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria for DCM, reclassified all detected variants in robust genes, and associated these results to patients' phenotype.

Methods: The study included 902 DCM probands from the Maastricht Cardiomyopathy Registry who underwent genetic testing.

Implications of Genetic Testing in Dilated Cardiomyopathy.

Background: Genetic analysis is a first-tier test in dilated cardiomyopathy (DCM). Electrical phenotypes are common in genetic DCM, but their exact contribution to the clinical course and outcome is unknown. We determined the prevalence of pathogenic gene variants in a large unselected DCM population and determined the role of electrical phenotypes in association with outcome.

De novo variants in CAMTA1 cause a syndrome variably associated with spasticity, ataxia, and intellectual disability.

Previously, intragenic CAMTA1 copy number variants (CNVs) have been shown to cause non-progressive, congenital ataxia with or without intellectual disability (OMIM#614756). However, ataxia, intellectual disability, and dysmorphic features were all incompletely penetrant, even within families. Here, we describe four patients with de novo nonsense, frameshift or missense CAMTA1 variants.

A mutation update for the FLNC gene in myopathies and cardiomyopathies.

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM).

Safety and efficacy of embolotherapy for severe hemorrhage after partial nephrectomy.

Background: Partial nephrectomy may be complicated by postoperative hemorrhage, which may be treated by transcatheter embolization.

Purpose: To assess the safety and efficacy of embolotherapy for hemorrhagic complications of partial nephrectomy and to analyze the potential correlation between multiple bleeding sites on angiography and surgical complexity.

Material And Methods: A cohort of 25 patients presenting with severe, postoperative bleeding after partial nephrectomy and treated with catheter-directed superselective embolization was included.

Mutations in PDLIM5 are rare in dilated cardiomyopathy but are emerging as potential disease modifiers.

Background: A causal genetic mutation is found in 40% of families with dilated cardiomyopathy (DCM), leaving a large percentage of families genetically unsolved. This prevents adequate counseling and clear recommendations in these families. We aim to identify novel genes or modifiers associated with DCM.

Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy.

Background: Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in patients with nonischemic dilated cardiomyopathy (DCM) and compared its incremental value on top of N-terminal prohormone of brain natriuretic peptide (NT-proBNP).

Methods And Results: A total of 149 metabolites were measured in plasma and urine samples of 273 patients with DCM and with varying stages of disease (patients with DCM and normal left ventricular reverse remodeling, n = 70; asymptomatic DCM, n = 72; and symptomatic DCM, n = 131).

Impact of Magnetic Resonance Imaging on Prostate Cancer Staging and European Association of Urology Risk Classification.

Objective: To investigate the impact of magnetic resonance imaging (MRI) information on clinical staging, risk stratification, and treatment recommendations for prostate cancer (PCa) according to the European Association of Urology (EAU) guidelines.

Methods: We performed a single-center analysis of 180 men with PCa, undergoing clinical staging by digital rectal examination (DRE) as well as MRI before their robot-assisted radical prostatectomy. Patients were stratified according to the EAU guidelines into 4 well-defined risk categories, based on their clinical T-stage assessed by either DRE or MRI.

Prevalence of Pathogenic Gene Mutations and Prognosis Do Not Differ in Isolated Left Ventricular Dysfunction Compared With Dilated Cardiomyopathy.

Background: Genetic evaluation is recommended in patients with unexplained dilated cardiomyopathy (DCM), but its diagnostic yield and prognostic relevance in unexplained isolated left ventricular dysfunction (LVdys) is unknown.

Methods And Results: A total of 127 LVdys and 262 DCM patients underwent genetic screening. Long-term outcome consisted of a combined end point of life-threatening arrhythmia, heart transplantation, and death.

Endovascular Management of Severe Arterial Haemorrhage After Radical Prostatectomy: A Case Series.

Purpose: The aim of this study is to assess the safety, effectiveness and long-term outcome of endovascular management of arterial haemorrhage after radical prostatectomy (RP).

Materials And Methods: Ten patients who received endovascular treatment for refractory bleeding after RP between January 2008 and December 2016 were retrospectively identified. Contrast-enhanced computed tomography (CT) was performed and followed by catheter-directed treatment by means of transarterial embolization (TAE) or stent graft placement.

Time-of-Travel Methods for Measuring Optical Flow on Board a Micro Flying Robot.

For use in autonomous micro air vehicles, visual sensors must not only be small, lightweight and insensitive to light variations; on-board autopilots also require fast and accurate optical flow measurements over a wide range of speeds. Using an auto-adaptive bio-inspired Michaelis-Menten Auto-adaptive Pixel (M 2 APix) analog silicon retina, in this article, we present comparative tests of two optical flow calculation algorithms operating under lighting conditions from 6 × 10 - 7 to 1 . 6 × 10 - 2 W·cm - 2 (i.

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands.

Hearing impairment (HI) is genetically heterogeneous which hampers genetic counseling and molecular diagnosis. Testing of several single HI-related genes is laborious and expensive. In this study, we evaluate the diagnostic utility of whole-exome sequencing (WES) targeting a panel of HI-related genes.

TRUS-MR Fusion Biopsy of the Prostate: Radiological and Histological Correlation.

Objective: Targeted magnetic resonance/ultrasound fusion prostate biopsy has been shown to improve the detection of high-grade prostate cancer and to reduce sampling errors. Our objective is to assess MR-TRUS targeted fusion biopsy versus standard biopsy for the detection of clinically significant tumors.

Materials And Methods: Patients were referred for abnormal digital rectal examination (DRE) or risen prostate-specific antigen (PSA).

Staging of prostatic carcinoma at 1.5-T MRI: correlation of a simplified MRI exam with whole-mount radical prostatectomy specimens.

Objective: To retrospectively analyze the accuracy of simplified multiparametric MRI at 1.5 T for local staging by using whole-mount-section histopathological analysis as the standard of reference.

Methods: 123 consecutive patients underwent T2 weighted, T1 weighted and diffusion-weighted MRI without endorectal coil prior to radical prostatectomy.

Correlation of the patient's reported outcome Inflammatory-RODS with an objective metric in immune-mediated neuropathies.

Background And Purpose: There is increasing interest in using patient-reported outcome measures (PROMs) in clinical studies to capture individual changes over time. However, PROMs have also been criticized because they are entirely subjective. Our objective was to examine the relationship between a subjective PROM and an objective outcome tool in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and gammopathy-related polyneuropathy (MGUSP).

Does ability to walk reflect general functionality in inflammatory neuropathies?

The "ability to walk" is considered a benchmark for good clinical recovery and prognosis, particularly in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, it has never been determined whether being "able to walk" represents general functionality. The purpose of this study was to examine whether the ability to walk outside independently reflects general functional improvement in patients with GBS, CIDP, and gammopathy-related neuropathy (MGUSP).