OBJECTIVE: Chronic infantile neurologic, cutaneous, articular (CINCA) syndrome, also known as @entity829 ( @entity829 ), is a dominantly @entity74 . Although heterozygous germline gain-of-function @entity5704 mutations are a known cause of this disease, conventional genetic analyses fail to detect disease-causing mutations in    40% of @entity1 . Since somatic @entity5704 mosaicism has been detected in several mutation-negative @entity829 / @entity829 @entity1 , we undertook this study to determine the precise contribution of somatic @entity5704 mosaicism to the etiology of @entity829 / @entity829 . METHODS: An international case-control study was performed to detect somatic @entity5704 mosaicism in @entity829 / @entity829 @entity1 who had shown no mutation during conventional sequencing. Subcloning and sequencing of @entity5704 was performed in these mutation-negative @entity829 / @entity829 @entity1 and their healthy relatives. Clinical features were analyzed to identify potential genotype-phenotype associations. RESULTS: Somatic @entity5704 mosaicism was identified in 18 of the 26 @entity1 (69.2%). Estimates of the level of mosaicism ranged from 4.2% to 35.8% (mean    SD 12.1    7.9%). Mosaicism was not detected in any of the 19 healthy relatives (18 of 26 @entity1 versus 0 of 19 relatives; P < 0.0001). In vitro functional assays indicated that the detected somatic @entity5704 mutations had disease-causing functional effects. No differences in @entity5704 mosaicism were detected between different cell lineages. Among nondescript clinical features, a lower incidence of @entity1032 was noted in @entity1 with somatic mosaicism. Genotype-matched comparison confirmed that @entity1 with somatic @entity5704 mosaicism presented with milder neurologic symptoms. CONCLUSION: Somatic @entity5704 mutations were identified in 69.2% of @entity1 with mutation-negative @entity829 / @entity829 . This indicates that somatic @entity5704 mosaicism is a major cause of @entity829 / @entity829 .

High incidence of @entity5704 somatic mosaicism in XXXX with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1032 :: ('MESH:D008607', 'Disease') :: ['mental retardation'] @entity5704 :: ('114548', 'Gene') :: ['NLRP3'] @entity74 :: ('MESH:D030342', 'Disease') :: ['inherited systemic autoinflammatory disease'] @entity829 :: ('MESH:D056587', 'Disease') :: ['CINCA syndrome', 'NOMID', 'neonatal-onset multisystem inflammatory disease']
@entity1 :: (9606,Species) :: ['patients']
