Single Center Experience in Next Generation Sequencing for Genetic Diagnosis of Autoinflammatory Disorders

Antonella Insalaco¹, Elisa Pisaneschi², Francesca Romana Lepri², Daniele Minervino², Virginia Messia¹, Manuela Pardeo³ and Fabrizio De Benedetti¹, ¹Division of Rheumatology, Department of Pediatric Medicine, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, ²Ospedale Pediatrico Bambino Gesù, IRCCS, Department of Cytogenetics, Roma, Italy, ³Department of Pediatric Medicine, Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Autoinflammatory Disease and genetics

Session Information

Date: Tuesday, November 10, 2015

Title: Pediatric Rheumatology - Pathogenesis and Genetics Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Autoinflammatory disorders (AIDs) represent an expanding group of complex diseases characterized by periodic or chronic systemic inflammations. Mutations in more than 15 genes have been associated with autoinflammatory recessive or dominant syndromes (1). Next Generation Sequencing (NGS) has emerged in the last year as new diagnostic tool in this field. to share data obtained by the application of NGS in a cohort of patients affected by an autoinflammatory disease of undefined origin evaluated at our center.

Methods: In this study we enrolled 158 patients evaluated at our center from 2010 to 2014. We developed NGS approache already known to be involved in AID (Panel 1: MVK, MEFV, NRLP12, NRLP3, NOD2, TNFRSF1A and PSTPIP1 and Panel 2: IL1RN, LPIN2, IL36RN, PSMB8). Targeted resequencing was performed using customized panel and analyzed with the MiSeq® sequencing platform (Illumina, San Diego, CA). All variants identified have been confirmed by Sanger sequencing.

Results: 48,73% of the patients present variants in genes of Panel 1. 32,46% have variants in NLRP3 gene: the most frequent variants are Q705K (56%) and V200M (32%). About 26% have variants in NOD2, the most frequent variant is R702W (25%). 30% have variants in NLRP12, the most frequent variant is F402L (65%), in two cases is homozygous. 23,37% have variants in MEFV, the most frequent variant is E148Q (22%). 4% have variants in MVK, V377I (100%). 10,38% have variants in TNFRSF1A, the most frequent variant is R121Q (75%). 9% have variants in PSTPIP1. 69% of the patients present variant in only one gene; 28,57% present variants in two different genes and two patients in three genes. We performed 15 familial study to unravel the segregation of some variants.

Conclusion: NGS leads to the identification of many genetic variants that could be associated with disease susceptibility. The major challenge is in the interpretation of the clinical relevance of identified variants (2). Some patients show variants in multiple analyzed genes: it can be assumed that different variants in different genes may cooperate to determine a pathological phenotype. This will necessitate large-scale population studies, in vitro functional assay and careful correlation of genetic information with phenotypic data (3). Crucial is, therefore, close collaboration with clinicians.

Disclosure: A. Insalaco, None; E. Pisaneschi, None; F. R. Lepri, None; D. Minervino, None; V. Messia, None; M. Pardeo, None; F. De Benedetti, None.

To cite this abstract in AMA style:

Insalaco A, Pisaneschi E, Lepri FR, Minervino D, Messia V, Pardeo M, De Benedetti F. Single Center Experience in Next Generation Sequencing for Genetic Diagnosis of Autoinflammatory Disorders [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/single-center-experience-in-next-generation-sequencing-for-genetic-diagnosis-of-autoinflammatory-disorders/. Accessed .

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