Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases

Rusmini, Marta; Federici, Silvia; Caroli, Francesco; Grossi, Alice; Baldi, Maurizia; Obici, Laura; Insalaco, Antonella; Tommasini, Alberto; Caorsi, Roberta; Gallo, Eleonora; Olivieri, Alma Nunzia; Marzano, AngeloValerio; Coviello, Domenico; Ravazzolo, Roberto; Martini, Alberto; Gattorno, Marco; Ceccherini, Isabella

doi:10.1136/annrheumdis-2015-207701

Cited by 63 publications

(39 citation statements)

References 32 publications

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“…A DNA target panel was created to identify possible disease‐causing mutations in 10 genes already known to be involved in autoinflammatory diseases, namely MEFV , MVK , TNFRSF1A , NLRP3 , NLRP12 , PSTPIP1 , NOD2 , PSMB8 , IL1RN and LPIN2 . Panel features, such as size and coverage, as well as library construction, amplification and subsequent sequencing on Ion 314 chips have already been reported . The analysis from raw FastQ sequencing data to variant call format tables of annotated variant calls was carried out using the Ion Torrent Alignment and the Ion Reporter 4.0 (Thermo Fisher), specific for data generated by PGM.…”

Section: Methodsmentioning

confidence: 99%

“…Panel features, such as size and coverage, as well as library construction, amplification and subsequent sequencing on Ion 314 chips have already been reported. 8 The analysis from raw FastQ sequencing data to variant call format tables of annotated variant calls was carried out using the Ion Torrent Alignment and the Ion Reporter 4.0 (Thermo Fisher), specific for data generated by PGM. Variants thus identified and believed to play a causal role were further validated by standard dideoxy sequencing (Sanger sequencing) using the BigDye Terminator v.3.1 Cycle Sequencing Kit (Thermo Fisher) and an ABI3730 automatic sequencer (Thermo Fisher), as previously reported.…”

Section: Genetic Analysismentioning

confidence: 99%

“…Variants thus identified and believed to play a causal role were further validated by standard dideoxy sequencing (Sanger sequencing) using the BigDye Terminator v.3.1 Cycle Sequencing Kit (Thermo Fisher) and an ABI3730 automatic sequencer (Thermo Fisher), as previously reported. 8…”

Section: Genetic Analysismentioning

confidence: 99%

See 2 more Smart Citations

Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)

et al. 2017

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Section: Methodsmentioning

confidence: 99%

Section: Genetic Analysismentioning

confidence: 99%

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Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)

et al. 2017

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“…Ceccherini et al compared the performance of three NGS platforms in a pilot study interrogating 10 genes ( MEFV, MVK, TNFRSF1A, NLRP3, NLRP12, NOD2, PSTPIP1, IL1RN, LPIN2 and PSMB8 ) from 50 cases with genetically confirmed autoinflammatory disorders [105]. The expected mutations were correctly called in most cases, although there was a failure to detect p.Val377Ile MVK in a number of cases due to low coverage.…”

Section: Genetic Sequencing Of Autoinflammatory Disordersmentioning

confidence: 99%

The classification, genetic diagnosis and modelling of monogenic autoinflammatory disorders

Moghaddas

Masters

2018

Clinical Science

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Monogenic autoinflammatory disorders are an increasingly heterogeneous group of conditions characterised by innate immune dysregulation. Improved genetic sequencing in recent years has led not only to the discovery of a plethora of conditions considered to be ‘autoinflammatory’, but also the broadening of the clinical and immunological phenotypic spectra seen in these disorders. This review outlines the classification strategies that have been employed for monogenic autoinflammatory disorders to date, including the primary innate immune pathway or the dominant cytokine implicated in disease pathogenesis, and highlights some of the advantages of these models. Furthermore, the use of the term ‘autoinflammatory’ is discussed in relation to disorders that cross the innate and adaptive immune divide. The utilisation of next-generation sequencing (NGS) in this population is examined, as are potential in vivo and in vitro methods of modelling to determine pathogenicity of novel genetic findings. Finally, areas where our understanding can be improved are highlighted, such as phenotypic variability and genotype–phenotype correlations, with the aim of identifying areas of future research.

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“…In recent years, with the use of WES, several undiagnosed Mendelian genetic conditions have been investigated in order to search the involved gene (155, 156). WES has been applied to the study of trios (unaffected parents and the sporadic case) and unrelated patients with phenotypic similarities.…”

Section: Genetic Diagnosis With New Technologiesmentioning

confidence: 99%

Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations, and Genotype/Phenotype Correlations

et al. 2017

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Autoinflammatory diseases (AIDs) are a genetically heterogeneous group of diseases caused by mutations of genes encoding proteins, which play a pivotal role in the regulation of the inflammatory response. In the pathogenesis of AIDs, the role of the genetic background is triggered by environmental factors through the modulation of the innate immune system. Monogenic AIDs are characterized by Mendelian inheritance and are caused by highly penetrant genetic variants in single genes. During the last years, remarkable progress has been made in the identification of disease-associated genes by using new technologies, such as next-generation sequencing, which has allowed the genetic characterization in undiagnosed patients and in sporadic cases by means of targeted resequencing of a gene panel and whole exome sequencing. In this review, we delineate the genetics of the monogenic AIDs, report the role of the most common gene mutations, and describe the evidences of the most sound genotype/phenotype correlations in AID.

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Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases

Cited by 63 publications

References 32 publications

Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)

Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)

The classification, genetic diagnosis and modelling of monogenic autoinflammatory disorders

Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations, and Genotype/Phenotype Correlations

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