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Getting to the Genetic Basis of Auto-inflammatory Syndromes
June 10 2015 3:46 PM ET — via RheumReports
Two lines of genetic investigations were very topical today at EULAR 2015. One was Next Generation Sequencing (NGS) and the other was epigenetics. Dr. Lepri and colleagues from Italy presented their experience assessing auto-inflammatory disorders using NGS. There are at least 15 genes affecting several distinct pathways that can lead to periodic or chronic systemic inflammation in the absence of autoimmune markers. Despite this recent success in the identifying the genetic basis of auto-inflammatory disorders, most patients have no clear genetic basis for their illness.
The investigators assessed 145 patients with auto-inflammatory disorders with undefined origin. Their protocol included interrogation of 11 known genes which were incorporated into two panels (MVK, MEFV, NRLP12, NRLP3, NOD2, TNFRSF1A and PSTPIP1) and (IN1RN, LPIN2, IL36RN and PSMB8). Targeted sequencing was performed using a customized panel and variants were confirmed with Sanger sequencing.
NGS analysis led to the identification of different variants in 40% of patients. 29% of patients had variants in two different genes. The three most common genes that showed variants were NLRP3 in 36%, NLRP12 in 31% and NOD2 in 19%.
This NGS protocol appears to have an impressive utility in identifying variants associated with auto-inflammatory disease of undetermined etiology. The major challenge now for clinicians is to identify the clinical relevance and utility of these variants. This is can only be done by additional large-scale genotype / phenotype correlation studies.
Reference:
SINGLE CENTER EXPERIENCE IN NEXT GENERATION SEQUENCING FOR GENETIC DIAGNOSIS OF AUTOINFLAMMATORY DISORDERS (AIDS) [OP0008]
F. R. Lepri1, E. Pisaneschi1,*, D. Minervino1, V. Messia2, M. Pardeo2, F. De Benedetti3, A. Insalaco2
1Cytogenetics and Molecular Genetics, Bambino Gesù Paediatric Hospital, IRCCS, 2Division of Rheumatology, Department of Paediatric Medicine, Bambino Gesù Children's Hospital, IRCCS, 3Division of Rheumatology, Department of Paediatric Medicine, Bambino Gesù Children's Hospital, Rome, Italy
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About the Author
Dr. Proton Rahman
Proton Rahman, MD is a Clinician Scientist at Memorial University of Newfoundland, where he is also Associate Dean of Clinical Research and a University Research Professor. He practices rheumatology at Eastern Health in St. John’s, Newfoundland.
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