Cryopyrin-associated Periodic Syndromes in Italian Patients: Evaluation of the Rate of Somatic NLRP3 Mosaicism and Phenotypic Characterization.
J Rheumatol
; 44(11): 1667-1673, 2017 Nov.
Article
en En
| MEDLINE
| ID: mdl-28916543
ABSTRACT
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Encéfalo
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Síndromes Periódicos Asociados a Criopirina
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Proteína con Dominio Pirina 3 de la Familia NLR
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Mosaicismo
Tipo de estudio:
Risk_factors_studies
Límite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
País/Región como asunto:
Europa
Idioma:
En
Revista:
J Rheumatol
Año:
2017
Tipo del documento:
Article