Four-year evaluation of neonatal cystic fibrosis screening in Southern Belgium.

Unlabelled: Newborn screening for cystic fibrosis (CF-NBS) using an IRT-DNA algorithm with a 12 CFTR-variant panel and an IRT/IRT failsafe was officially implemented in the French-speaking Community of Belgium in January 2020. This screening protocol was evaluated after 4 years according to the criteria defined by the European Cystic Fibrosis Society's working group on neonatal screening. Immunoreactive trypsinogen concentration (IRT) was measured on dried blood spots collected between the second and the fourth day of life.

[Neonatal screening for cystic fibrosis in the Liège region : first evaluation after 4 years].

Since January 2020, neonatal screening for cystic fibrosis (CF-NBS) has been implemented in the Wallonia-Brussels Federation. It's based on the immunoreactive trypsin (IRT1) assay between day 2 and day 4, associated with a 12 CFTR pathogenic variants analysis and with an IRT control on day 21. The aim of this study is to evaluate the performance of our CF-NBS in Liège according to the quality criteria defined by the European Cystic Fibrosis Society's working group on neonatal screening.

Association between executive functions and COMT Val108/158Met polymorphism among healthy younger and older adults: A preliminary study.

Background And Objectives: Genetic variability in the dopaminergic system could contribute to age-related impairments in executive control. In this study, we examined whether genetic polymorphism for catechol-O-methyltransferase (COMT Val158Met) is related to performance on updating, shifting and inhibition tasks.

Methods: We administered a battery of executive tasks assessing updating, shifting and inhibition functions to 45 older and 55 younger healthy participants, and created composite z-scores associated to each function.

Dutch founder SDHB exon 3 deletion in patients with pheochromocytoma-paraganglioma in South Africa.

Objective: Screening studies have established genetic risk profiles for diseases such as multiple endocrine neoplasia type 1 (MEN1) and pheochromocytoma-paraganglioma (PPGL). Founder effects play an important role in the regional/national epidemiology of endocrine cancers, particularly PPGL. Founder effects in the Netherlands have been described for various diseases, some of which established themselves in South Africa due to Dutch emigration.

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium.

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries.

Frequency of Participation in External Quality Assessment Programs Focused on Rare Diseases: Belgian Guidelines for Human Genetics Centers.

Background: Participation in quality controls, also called external quality assessment (EQA) schemes, is required for the ISO15189 accreditation of the Medical Centers of Human Genetics. However, directives on the minimal frequency of participation in genetic quality control schemes are lacking or too heterogeneous, with a possible impact on health care quality.

Objective: The aim of this project is to develop Belgian guidelines on the frequency of participation in quality controls for genetic testing in the context of rare diseases.

Newborn screening of duchenne muscular dystrophy specifically targeting deletions amenable to exon-skipping therapy.

Duchenne Muscular Dystrophy (DMD) is a lethal progressive muscle-wasting disease. New treatment strategies relying on DMD gene exon-skipping therapy have recently been approved and about 30% of patients could be amenable to exon 51, 53 or 45 skipping. We evaluated the spectrum of deletions reported in DMD registries, and designed a method to screen newborns and identify DMD deletions amenable to exon 51, 53 and 45 skipping.

Pancreatic Neuroendocrine Neoplasm Associated with a Familial MAX Deletion.

Most pancreatic neuroendocrine neoplasms (pNEN) occur sporadically but they can also occur as part of multiple endocrine neoplasia type 1 (MEN1). was originally described as an inherited pheochromocytoma-paraganglioma risk gene, but also has recently been implicated in pituitary tumorigenesis. Here we describe the first case of a pNEN associated with an inherited gene deletion in a family with endocrine tumors.

[(S)un (M)ay (A)rise on SMA : the hope of a region without spinal muscular atrophy].

The treatment of spinal muscular atrophy (SMA) has considerably changed over the last 3 years. Several approaches that aim to increase the deficient SMN protein have demonstrated an efficacy that is inversely correlated with disease duration. In this context, newborn screening (NBS) is increasingly considered as the next step in several countries or regions.

Newborn screening for SMA in Southern Belgium.

Approval was recently granted for a new treatment for spinal muscular atrophy (SMA). Given that the treatment is effective when administered early and the societal burden of SMA-related disability, the implementation of a newborn screening program is warranted. We describe the stepwise process that led us to launch a newborn screening program for SMA in Southern Belgium.

A next-generation newborn screening pilot study: NGS on dried blood spots detects causal mutations in patients with inherited metabolic diseases.

The range of applications performed on dried blood spots (DBS) widely broadened during the past decades to now include next-generation sequencing (NGS). Previous publications provided a general overview of NGS capacities on DBS-extracted DNA but did not focus on the identification of specific disorders. We thus aimed to demonstrate that NGS was reliable for detecting pathogenic mutations on genomic material extracted from DBS.

[PHARMACOGENOMICS AND PERSONALIZED MEDICINE: TOWARDS A SYSTEMATIC GENOMIC SCREENING?].

Recent advances in medical genomics open new perspectives for personalized medicine through the identification of genetic variants that influence drug response and/or the risk of side effects. Today, the clinical applications of pharmacogenetics remain scarce as a consequence of the cost and turn-around-time of genetic tests. However, a few tests are recommended, for instance before the prescription of some anti-cancer agents or the anti-retroviral agent abacavir.

Mutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy.

Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive leukoencephalopathy. Homozygosity mapping, whole exome sequencing, and functional studies were used to define the underlying molecular defect.

Modulating effect of COMT Val(158)Met polymorphism on interference resolution during a working memory task.

Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15years, in particular as a potential modulator of the neural substrates underlying inhibitory processes and updating in working memory (WM). In an event-related functional magnetic resonance imaging (fMRI) study, we administered a modified version of the Sternberg probe recency task (Sternberg, 1966) to 43 young healthy volunteers, varying the level of interference across successive items. The task was divided into two parts (high vs.

Influence of COMT Genotype on Antero-posterior Cortical Functional Connectivity Underlying Interference Resolution.

Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val(158)Met) has received increasing attention as a possible modulator of executive functioning and its neural correlates. However, this attention has generally centered on the prefrontal cortices because of the well-known direct impact of COMT enzyme on these cerebral regions. In this study, we were interested in the modulating effect of COMT genotype on anterior and posterior brain areas underlying interference resolution during a Stroop task.

Array-CGH analysis in Rwandan patients presenting development delay/intellectual disability with multiple congenital anomalies.

Background: Array-CGH is considered as the first-tier investigation used to identify copy number variations. Right now, there is no available data about the genetic etiology of patients with development delay/intellectual disability and congenital malformation in East Africa.

Methods: Array comparative genomic hybridization was performed in 50 Rwandan patients with development delay/intellectual disability and multiple congenital abnormalities, using the Agilent's 180 K microarray platform.

Genetic diagnosis of Duchenne and Becker muscular dystrophy using multiplex ligation-dependent probe amplification in Rwandan patients.

Duchenne and Becker muscular dystrophies are the most common clinical forms of muscular dystrophies. They are genetically X-linked diseases caused by a mutation in the dystrophin (DMD) gene. A genetic diagnosis was carried out in six Rwandan patients presenting a phenotype of Duchenne and Becker muscular dystrophies and six asymptomatic female carrier relatives using multiplex ligation-dependent probe amplification (MLPA).

Modulating effect of COMT genotype on the brain regions underlying proactive control process during inhibition.

Introduction: Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val(158)Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions.

Methods: In an event-related functional magnetic resonance imaging (fMRI) study, a modified version of the Stroop task was administered to three groups of 15 young adults according to their COMT Val(158)Met genotype [Val/Val (VV), Val/Met (VM) and Met/Met (MM)]. Based on the theory of dual mechanisms of control (Braver et al.

Concurrent synaptic and systems memory consolidation during sleep.

Memories are consolidated during sleep by two apparently antagonistic processes: (1) reinforcement of memory-specific cortical interactions and (2) homeostatic reduction in synaptic efficiency. Using fMRI, we assessed whether episodic memories are processed during sleep by either or both mechanisms, by comparing recollection before and after sleep. We probed whether LTP influences these processes by contrasting two groups of individuals prospectively recruited based on BDNF rs6265 (Val66Met) polymorphism.

Evidence of association between interferon regulatory factor 5 gene polymorphisms and asthma.

Asthma is a heterogeneous disorder hallmarked by chronic inflammation in the respiratory system. Exacerbations of asthma are correlated with respiratory infections. Considering the implication of interferon regulatory factor 5 (IRF5) in innate and adaptive immunity, we investigated the preferential transmission patterns of ten IRF5 gene polymorphisms in two asthmatic family cohorts.

Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity.

Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia.

IL28B polymorphism and the control of hepatitis C virus infection: ready for clinical use?

Polymorphisms in the region of the interleukin-28B (IL28B) gene have recently been associated with spontaneous and treatment induced clearance of hepatitis C virus infection. The specific mechanisms of how IL28B polymorphisms affect HCV suppression remain unknown. It is a matter of ongoing debate how to incorporate the IL28B data into the current treatment algorithms with pegylated interferon-alpha and ribavirin.