Published 2017
| Version v1
Publication
Cryopyrin-associated periodic syndromes in Italian Patients: Evaluation of the rate of somatic NLRP3 mosaicism and phenotypic characterization
Creators
- Lasiglie D.
- Mensa-Vilaro A.
- Ferrera D.
- Caorsi R.
- Penco F.
- Santamaria G.
- Di Duca M.
- Amico G.
- Nakagawa K.
- Antonini F.
- Tommasini A.
- Consolini R.
- Insalaco A.
- Cattalini M.
- Obici L.
- Gallizzi R.
- Santarelli F.
- Del Zotto G.
- Severino M.
- Rubartelli A.
- Ravazzolo R.
- Martini A.
- Ceccherini I.
- Nishikomori R.
- Gattorno M.
- Arostegui J. I.
- Borghini S.
Contributors
Others:
- Lasiglie, D.
- Mensa-Vilaro, A.
- Ferrera, D.
- Caorsi, R.
- Penco, F.
- Santamaria, G.
- Di Duca, M.
- Amico, G.
- Nakagawa, K.
- Antonini, F.
- Tommasini, A.
- Consolini, R.
- Insalaco, A.
- Cattalini, M.
- Obici, L.
- Gallizzi, R.
- Santarelli, F.
- Del Zotto, G.
- Severino, M.
- Rubartelli, A.
- Ravazzolo, R.
- Martini, A.
- Ceccherini, I.
- Nishikomori, R.
- Gattorno, M.
- Arostegui, J. I.
- Borghini, S.
Description
Objective: To evaluate the rate of somatic NLRP3 mosaicism in an Italian cohort of mutation-negative patients with cryopyrin-associated periodic syndrome (CAPS). Methods: The study enrolled 14 patients with a clinical phenotype consistent with CAPS in whom Sanger sequencing of the NLRP3 gene yielded negative results. Patients' DNA were subjected to amplicon-based NLRP3 deep sequencing. Results: Low-level somatic NLRP3 mosaicism has been detected in 4 patients, 3 affected with chronic infantile neurological cutaneous and articular syndrome and 1 with Muckle-Wells syndrome. Identified nucleotide substitutions encode for 4 different amino acid exchanges, with 2 of them being novel (p.Y563C and p.G564S). In vitro functional studies confirmed the deleterious behavior of the 4 somatic NLRP3 mutations. Among the different neurological manifestations detected, 1 patient displayed mild loss of white matter volume on brain magnetic resonance imaging. Conclusion: The allele frequency of somatic NLRP3 mutations occurs generally under 15%, considered the threshold of detectability using the Sanger method of DNA sequencing. Consequently, routine genetic diagnostic of CAPS should be currently performed by next-generation techniques ensuring high coverage to identify also low-level mosaicism, whose actual frequency is yet unknown and probably underestimated. The Journal of Rheumatology
Additional details
Identifiers
- URL
- http://hdl.handle.net/11567/965146
- URN
- urn:oai:iris.unige.it:11567/965146
Origin repository
- Origin repository
- UNIGE