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Next-generation sequencing identifies new variants in autoinflammatory diseases
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New genetic variants and polymorphisms were identified using next-generation sequencing in patients with autoinflammatory diseases, according to study findings presented at the European League Against Rheumatism Annual European Congress of Rheumatology.
Researchers enrolled 145 patients with undefined autoinflammatory diseases who were evaluated between 2010 and 2014 at a single center in Rome. Next-generation sequencing (NGS) was used to identify 11 genes with a known association with autoinflammatory diseases in two panels; panel one comprised MVK, MEFV, NRLP12, NRLP3, NOD2, TNFRSF1A and PSTPIP1, and panel two comprised IL1RN, LPIN2, IL36RN and PSMB8. A custom, unique panel was used to perform targeted resequencing with the MiSeq sequencing platform (Illumina), and variants were confirmed by Sanger sequencing. When possible, variants of known family members were also sequenced to study segregation.
After NGS analysis, variants from panel one were identified in 61 patients at a detection rate of 42%. Variants were detected in the NLRP3 gene in 36% of patients, in the NOD2 in 19% of patients, in the NLRP12 in 31%, in the MEFV in 23% of patients, in the MVK and TNFRSF1A in 8% of patients, and in the PSTPIP1 in 6% of patients.
Some of the variants were new, whereas others were polymorphisms or known variants. Additionally, some of the variants may occur infrequently but in more than 1% of the population, making it challenging to determine their clinical relevance, whereas others may be described as risk factors, according to the researchers.
“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,” the researchers wrote. “This will necessitate large-scale population studies, in vitro functional assay and careful correlation of genetic information with phenotypic data.”
Close collaboration with clinicians was described as “crucial” by the researchers. – by Shirley Pulawski
Reference:
Lepri FR, et al. Paper #OP0008. Presented at: European League Against Rheumatism Annual European Congress of Rheumatology; June 10-13, 2015; Rome.
Disclosure: The researchers report no relevant financial disclosures.