Christophe Beroud

Christophe Beroud
  • Pharm D, PhD
  • Professor at Aix-Marseille University

About

261
Publications
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16,723
Citations
Current institution
Aix-Marseille University
Current position
  • Professor

Publications

Publications (261)
Article
Background The von Hippel-Lindau (VHL) disease is a hereditary tumour syndrome caused by germline mutations in VHL tumour suppressor gene. The identification of VHL variants requires accurate classification which has an impact on patient management and genetic counselling. Methods The TENGEN (French oncogenetics network of neuroendocrine tumors) a...
Article
Full-text available
SLC40A1 is the sole iron export protein reported in mammals and is a key player in both cellular and systemic iron homeostasis. This unique iron exporter, which belongs to the major facilitator superfamily, is predominantly regulated by the hyposideremic hormone hepcidin. SLC40A1 dysfunction causes ferroportin disease, and autosomal dominant iron o...
Preprint
Copy number variants (CNVs) are a major cause of rare pediatric diseases with a broad spectrum of phenotypes. Genetic diagnosis based on comparative genomic hybridization tests typically identifies ~8-10% of patients as having CNVs of unknown significance, revealing the current limits of clinical interpretation. The adoption of whole-genome sequenc...
Article
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Background: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early-onset epileptic encephalopathy and/or chorea. Objective: The aim was to characterize the clinical and genetic features of patients with mild GNAO1-related phenotype with prominent movement disorders. Methods: We included patients diagno...
Article
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Background LAMA2-related muscular dystrophy (LAMA2-RD) encompasses a group of recessive muscular dystrophies caused by mutations in the LAMA2 gene, which codes for the alpha-2 chain of laminin-211 (merosin). Diagnosis is straightforward in the classic congenital presentation with no ambulation and complete merosin deficiency in muscle biopsy, but i...
Article
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Background Facioscapulohumeral muscular dystrophy (FSHD) is among the most prevalent muscular dystrophies and currently has no treatment. Clinical and genetic heterogeneity are the main challenges to a full comprehension of the physiopathological mechanism. Improving our knowledge of FSHD is crucial to the development of future therapeutic trials a...
Article
Full-text available
Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or con...
Article
Background The difficulty in interpreting somatic alterations is correlated with the increase in sequencing panel size. To correctly guide the clinical management of patients with cancer, there needs to be accurate classification of pathogenicity followed by actionability assessment. Here, we describe a specific detailed workflow for the classifica...
Article
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In skeletal muscle, long noncoding RNAs (lncRNAs) are involved in dystrophin protein stabilization but also in the regulation of myocytes proliferation and differentiation. Hence, they could represent promising therapeutic targets and/or biomarkers for Duchenne and Becker muscular dystrophy (DMD/BMD). DMD and BMD are X-linked myopathies characteriz...
Article
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Copy number variations (CNVs) are major causative contributors both in the genesis of genetic diseases and human neoplasias. While “High-Throughput” sequencing technologies are increasingly becoming the primary choice for genomic screening analysis, their ability to efficiently detect CNVs is still heterogeneous and remains to be developed. The aim...
Article
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Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterio...
Article
Full-text available
Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterio...
Article
Full-text available
Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterio...
Article
Full-text available
Background: Canine models of Duchenne muscular dystrophy (DMD) are a valuable tool to evaluate potential therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been described in canines, but the Golden Retriever muscular dystrophy (GRMD) model remains the most used in preclinical studies. Here, we r...
Preprint
Full-text available
Background Canine models of Duchenne muscular dystrophy (DMD) are valuable to evaluate therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been described in canines, but the GRMD (Golden Retriever Muscular Dystrophy) model remains the one used in most preclinical studies. Methods We report a new s...
Preprint
Full-text available
Background Canine models of Duchenne muscular dystrophy (DMD) are a valuable tool to evaluate potential therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been described in canines, but the GRMD (Golden Retriever Muscular Dystrophy) model remains the most used in preclinical studies. Here we repo...
Article
Background: Aortic risk has not been evaluated in patients with Marfan syndrome and documented pathogenic variants in the FBN1 gene. Objectives: This study sought to describe aortic risk in a population with Marfan syndrome with pathogenic variants in the FBN1 gene as a function of aortic root diameter. Methods: Patients carrying an FBN1 patho...
Preprint
Full-text available
Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterio...
Article
Charcot-Marie-Tooth disease (CMT) is a hereditary sensory-motor neuropathy characterized by a strong clinical and genetic heterogeneity. Over the past few years, with the occurrence of whole-exome sequencing (WES) or whole-genome sequencing (WGS), the molecular diagnosis rate has been improved by allowing the screening of more than 80 genes at one...
Article
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Full-text available
Human genomics is undergoing a step change from being a predominantly research-driven activity to one driven through health care as many countries in Europe now have nascent precision medicine programmes. To maximize the value of the genomic data generated, these data will need to be shared between institutions and across countries. In recognition...
Article
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In 2015, the ACMG‐AMP guidelines provided a general procedure for the objective and reproducible classification of genomic variants. While the benefits of this framework are of major importance, its adaptation for locus‐specific use is needed. Multiple Endocrine Neoplasia type 1 (MEN1) occurs due to inactivating mutations in the tumour suppressor g...
Article
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Background: Both bicuspid aortic valve (BAV) and Marfan syndrome have been associated with aortic dissection risk, but it is unknown whether the presence of BAV is associated with an increased aortic risk in patients with an FBN1 gene mutation. We evaluated aortic diameters, aortic valve function, and aortic shape in Marfan syndrome patients with...
Article
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Background Facioscapulohumeral muscular dystrophy is a rare inherited neuromuscular disease with an estimated prevalence of 1/20,000 and France therefore harbors about 3000 FSHD patients. With research progress and the development of targeted therapies, patients’ identification through registries can facilitate and improve recruitment in clinical t...
Article
Context Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the MEN1 gene characterized by a broad spectrum of clinical manifestations, of which the most frequent are primary hyperparathyroidism, pituitary adenomas, and neuroendocrine tumors. Objective The aim of this work is to facilitate interpretat...
Article
Flagella and motile cilia share a 9 + 2 microtubule-doublet axoneme structure, and asthenozoospermia (reduced spermatozoa motility) is found in 76% of men with primary ciliary dyskinesia (PCD). Nevertheless, causal genetic variants in a conserved axonemal component have been found in cases of isolated asthenozoospermia: 30% of men with multiple mor...
Article
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With the rapidly developing high-throughput sequencing technologies known as next generation sequencing or NGS, our approach to gene hunting and diagnosis has drastically changed. In <10 years, these technologies have moved from gene panel to whole genome sequencing and from an exclusively research context to clinical practice. Today, the limit is...
Article
Objectives: Inherited myopathies are major causes of muscle atrophy and are often characterized by rigid spine syndrome, a clinical feature designating patients with early spinal contractures. We aim to present a decision algorithm based on muscular whole body magnetic resonance imaging (mWB-MRI) as a unique tool to orientate the diagnosis of each...
Article
Background: Exacerbation of hyperkinesia is a life-threatening complication of dyskinetic movement disorders, which can lead to multi-organ failure and even to death. GNAO1 has been recently identified to be involved in the pathogenesis of early infantile epileptic encephalopathy and movement disorders. Patients with GNAO1 mutations can present wi...
Article
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Context Circulating Rare Cells (CRC) are non-haematological cells circulating in blood. They include Circulating Cancer Cells (CCC) and cells with uncertain malignant features (CRC-UMF) according to cytomorphology. Clear cell renal cell carcinomas frequently bear a mutated Von Hippel-Lindau (VHL) gene. Aim To match blind genetic analysis of CRC an...
Article
Tricho-Hepato-Enteric syndrome (THES) is a very rare autosomal recessive syndromic enteropathy caused by mutations of either TTC37 or SKIV2L genes. Very little is known of these two gene products in mammals nor of the pathophysiology of the disease. Since the identification of the genes, we have set up the molecular diagnostic of THES in routine, g...
Article
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Background: Recent short-term clinical trials in patients with Duchenne Muscular Dystrophy (DMD) have indicated greater disease variability in terms of progression than expected. In addition, as average life-expectancy increases, reliable data is required on clinical progression in the older DMD population. Objective: To determine the effects of...
Chapter
Almost 25 years ago a first attempt was made to decipher the various steps of colorectal tumor development. It led to the creation of a model of colorectal tumorigenesis in which the steps required for the development of cancer involve the mutational activation of an oncogene coupled with the loss of several tumor suppressor genes. This model relie...
Article
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Splenic diffuse red pulp lymphoma is an indolent small B-cell lymphoma recognised as a provisional entity in the WHO 2008 classification. Its precise relationship with other related splenic B-cell lymphomas with frequent leukaemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore...
Article
Introduction: Oncogenetics is a long-term process, which requires a close relation between patients and medical teams, good familial links allowing lifetime follow-up. Numerous documents are exchanged in between the medical team, which has to frequently interact. We present here a new tool that has been conceived specifically for this management....
Article
Background.: Visceral leishmaniasis (Kala-azar, KA) is the most severe form of leishmaniasis, characterized by fever, weight loss, hepatosplenomegaly and lymphadenopathy. During an outbreak of KA in Babar El Fugara (Sudan), 5.7% of cured patients displayed relapses, with familial clustering in half of the cases. Methods.: We performed whole-exom...
Article
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Background Deficiency in dihydropyrimidine dehydrogenase (DPD) enzyme is the main cause of severe and lethal fluoropyrimidine-related toxicity. Various approaches have been developed for DPD-deficiency screening, including DPYD genotyping and phenotyping. The goal of this prospective observational study was to perform exhaustive exome DPYD sequenci...
Data
Location of exonic DPYD variants relative to DPD protein. (TIF)
Data
Description of maximal toxicity grade over cycles 1–2 (CTCAE v3 criteria). (DOC)
Data
Pairwise linkage disequilibria (LD) between bi-allelic DPYD variants. (TIF)
Article
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Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases mig...
Article
Background: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance and metabolic abnormalities. This syndrome is caused by heterozygous de novo mutations in the POLD1 gene. To date, 19 p...
Article
Introduction La pneumopathie interstitielle diffuse (PID) est l’une des causes majeure de mortalité chez les patients atteints de polyarthrite rhumatoïde (PR). Malgré une prévalence et une mortalité importante, la physiopathologie de la PID associée à la PR (PR-PID) reste méconnue. La PR-PID partage plusieurs caractéristiques phénotypiques avec la...
Article
Significant advances have been made in recent years in the assessment and interpretation of the non-coding DNA that comprises 98% of our genome. Studying non-coding variants helps us better understand gene regulation and expression, non-coding RNA, and other non-coding genome functions. The 2016 annual scientific meeting of the Human Genome Variati...
Article
On the cover: With the rapid growth of NGS applications, we have devoted a full Human Mutation Special Issue to this topic. This unique edition addresses all aspects of the technology and its application, ranging from data generation/variant detection and interpretation to applications in the clinical context and legal/ethical aspects. Future techn...
Article
As next generation sequencing (NGS) increases access to human genetic variation, the challenge of determining clinical significance of variants becomes ever more acute. Germline variants in the BRCA1 and BRCA2 genes can confer substantial lifetime risk of breast and ovarian cancer. Assessment of variant pathogenicity is a critical part of clinical...
Article
High-throughput sequencing technologies have become fundamental for the identification of disease-causing mutations in human genetic diseases both in research and clinical testing contexts. The cumulative number of genes linked to rare diseases is now close to 3,500 with more than 1,000 genes identified between 2010 and 2014 thanks to the early ado...
Article
Adoption of next generation sequencing (NGS) in a diagnostic context raises numerous questions with regard to identification and reports of secondary variants (SVs) in actionable genes. To better understand the whys and wherefores of these questioning, it is necessary to understand how they are selected during the filtering process and how their pr...
Article
High-throughput next-generation sequencing such as whole-exome and whole-genome sequencing are being rapidly integrated into clinical practice. The use of these techniques leads to the identification of secondary variants for which decisions about the reporting or not to the patient need to be made. The American College of Medical Genetics and Geno...
Article
The 2016 scientific meeting of the Human Genome Variation Society (HGVS; http://www.hgvs.org) was held on the 20th of May in Barcelona, Spain, with the theme of “Clinical Interpretation of Variants from Next - Generation Sequencing”. The meeting was opened by William S. Oetting, of the University of Minnesota, United States. “Precision medicine” is...
Data
Figure S1: Multiple alignments of the Glutamic acid residue (E) at position 1003 of the FBN1 gene transcript ENST00000316623. Red square: surrounding windows of 3 residues used to remove species with more than one substitution per window. Thus Mouse, Rat, and all species below Armadillo were excluded. The remaining 55 species were used to compute t...
Article
Full-text available
Whole Exome Sequencing (WES) is increasingly applied to research and clinical diagnosis of human diseases. It typically results in large amounts of genetic variations. Depending on the mode of inheritance, only one or two correspond to pathogenic mutations responsible for the disease and present in affected individuals. Therefore it is crucial to f...
Article
Full-text available
Background: Laminin α2 deficient congenital muscular dystrophy, caused by mutations in the LAMA2 gene, is characterized by early muscle weakness associated with abnormal white matter signal on cerebral MRI. Objective: To report on 4 patients with LAMA2 gene mutations whose original clinical features complicated the diagnosis strategy. Methods: Clin...
Article
Full-text available
Massively parallel sequencing is rapidly becoming a widely used method in genetic diagnostics. However, there is still no clear consensus as to which approach can most efficiently identify the pathogenic mutations carried by a given patient, while avoiding false negative and false positive results. We developed a targeted exome approach (MyoPanel2)...
Article
Full-text available
The Gardos channel is a Ca(2+) sensitive, intermediate conductance, potassium selective channel expressed in several tissues including erythrocytes and pancreas. In normal erythrocytes, it is involved in cell volume modification. Here, we report the identification of a dominantly inherited mutation in the Gardos channel in 2 unrelated families and...
Article
Full-text available
Analysing the type and frequency of patient specific mutations that give rise to Duchenne Muscular Dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning and improved clinical care. Locus specific databases (LSDBs) allow for the collection, organization, storage and analysis of genetic variants of disease....
Article
Full-text available
Distal myopathies are a heterogeneous group of muscle diseases sharing the clinical pattern of predominant weakness in the feet and/or hands. The classical approach for molecular diagnosis is based on targeted gene-by-gene analysis guided by currently existing combinatorial algorithms.1 Many patients remain undiagnosed. Within the last 5 years, nex...
Article
The list of rare inherited disorders with renal involvement is rapidly growing. Many are single gene diseases affecting children, but cases are not restricted to pediatrics and diagnosis is often difficult and delayed. The expanding use of next-generation sequencing techniques is expected to discover new diseases, to challenge the definition of rar...
Article
Purpose: To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients. Design: Retrospective clinical and molecular genetic study. Methods: Clinical investigations incl...
Article
Missense, iso-semantic and intronic mutations are challenging for interpretation in particular for their impact in mRNA. Various tools such as the Human Splicing Finder system (HSF) could be used to predict the impact on splicing, however no diagnosis result could rely on predictions alone, but requires functional testing. Here we report an in vitr...
Article
Full-text available
Dysferlinopathies are a group of autosomal recessive muscular dystrophies caused by mutations in the dysferlin gene. This study presents clinical features and the mutational spectrum in the largest cohort of Chinese patients analyzed to date. A total of 36 unrelated Chinese patients with diagnostic suspicion of dysferlinopathy were clinically and g...
Article
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Des mutations dans le gène DYSF conduisent à l'absence complète ou partielle de la dysferline dans les muscles squelettiques. Elles sont à l'origine des dysferlinopathies primaires, un groupe clinique très hétérogène de maladies neuromusculaires rares à transmission autosomique récessive. Le diagnostic clinique de ces pathologies nécessite une conf...
Article
Full-text available
Research into rare diseases is typically fragmented by data type and disease. Individual efforts often have poor interoperability and do not systematically connect data across clinical phenotype, genomic data, biomaterial availability, and research/trial data sets. Such data must be linked at both an individual-patient and whole-cohort level to ena...
Article
Familial adenomatous polyposis (FAP) is a rare autosomal inherited disease that highly predisposes to colorectal cancer, characterized by a diffuse duodenal and colorectal polyposis associated with various extradigestive tumors and linked to germline mutations within the APC gene. A French consortium of laboratories involved in APC mutation screeni...
Article
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Correction After publication of this work [1], we noted that we inadvertently failed to include important Acknowledgments in our final version of the manuscript. Acknowledgements The authors received funding from the Australian National Health and Medical Research Council (APP1055319) and EU FP7 Project (HEALTH.2012.2.1.1-1-C): RD Connect: An integ...
Article
Full-text available
Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generati...
Article
Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical as well genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next gene...
Article
Full-text available
Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. While many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence < 5/1...
Article
Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterised by the degeneration of motor neurons and progressive muscle weakness. It is caused by homozygous deletions in the survival motor neuron gene on chromosome 5. SMA shows a wide range of clinical severity, with SMA type I patients often dying before 2 years of age,...
Patent
The present invention provides a method for determining all the molecular causes of Inherited Neuromuscular Disorders comprising determining a number of copy number variation(s), and/or determining a number of point mutation(s) on a physiological sample comprising a genome of a subject.
Article
The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12years enabled clarification of the natural his...
Article
Full-text available
Lynch syndrome is an autosomal dominant disease caused by germ line heterozygous mutations mainly involving the MSH2, MLH1 and MSH6 genes that belong to the DNA MisMatch Repair (MMR) genes family. The French network counting the 16 licensed laboratories involved in Lynch syndrome genetic testing developed three locus-specific databases with the UMD...
Article
Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapp...

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