Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

<p>Abstract</p> <p>Background</p> <p>Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.</p> <p>Methods</p> <p>We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).</p> <p>Results</p> <p>Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.</p> <p>Conclusions</p> <p>Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.</p

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Six pieds sous terre. Les cercueils en plomb d'époque romaine du musée des Antiquités de Rouen

National audienceCet article retrace l'histoire de la remarquable collection de cercueils en plomb du musée des Antiquités de Rouen, découverts à la faveur de grands travaux urbains au cours du XIXe siècle

Briga : aux confins septentrionaux de l'Empire, une ville romaine se révèle, Catalogue de l’exposition "Quand la Normandie était romaine. Briga, une ville retrouvée" organisée au Musée des Antiquités Rouen Métropole, 26 décembre 2020 - 20 juin 2021 / Chapelle du collège des Jésuites d’Eu, 24 juillet 2021 - 31 octobre 2021

International audienceLa Normandie se distingue parmi l’un des plus riches territoires du nord de la France dotés de vestiges d’époque romaine. Au cœur de la forêt d’Eu, des fouilles entamées en 2006 par le Service régional d’archéologie de Normandie révèlent au rythme des investigations les secrets d’une agglomération.Depuis leur redécouverte à la fin du XVIIIe siècle, les vestiges situés au lieu-dit du Bois-l’Abbé (Eu, Seine-Maritime) n’ont cessé de passionner curieux, érudits et chercheurs. Ceux-ci y ont d’ailleurs entrepris des fouilles ponctuelles jusqu’au début du XXIe siècle, principalement sur deux monuments interprétés jusqu’alors comme ceux d’un grand lieu de culte.Les recherches très actives poursuivies depuis une quinzaine d’années documentent désormais la naissance et le développement d’une ville antique aux origines gauloises, située au nord-ouest de l’Empire romain. Cette ville, longtemps oubliée sous le couvert forestier, s’appelait... Briga

« Statuette de Mercure et son socle » , in: « Regards sur les collections »

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Curieuse collection. À la recherche du Rouen gallo-romain.

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Curieuse collection. À la recherche du Rouen gallo-romain.

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Recherche de solutions nouvelles pour limiter les interactions entre le bois et l’eau

Publication sans comité de relectur