<i>CIAS1</i> Mutation in a Patient with Overlap between Muckle-Wells and Chronic Infantile Neurological Cutaneous and Articular Syndromes

Abstract

The Muckle-Wells syndrome is a rare autosomal dominant disorder belonging to the group of hereditary fever syndromes. The chronic infantile neurological cutaneous and articular (CINCA) syndrome is a systemic inflammatory disorder of unknown etiology with neonatal onset. They are considered as two different entities. We report the case of a 36-year-old man suffering since birth from a nonpruritic generalized urticaria, with inflammatory flares, joint manifestations and progressive deafness requiring a bilateral hearing aid. An initial diagnosis of Muckle-Wells syndrome was made. However, the patient had an unusual clinical presentation with slightly dysmorphic facial appearance, clubbing of the fingers, mild mental retardation and papilledema. After a genetic advice, a diagnosis of CINCA syndrome was made. Search for mutations in the CIAS1 gene revealed a new mutation in a heterozygous state. This case report really raises the question of a link between these two inflammatory diseases. Further studies are needed to confirm the involvement of mutations of the CIAS1 gene in CINCA syndrome.

Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU

“…13 D303G was found in P13, but a different transition at the same residue, D303N, was previously observed in 2 members of a family and 1 sporadic occurrence of CINCA/MWS overlapping phenotype and in 1 patient with CINCA syndrome. 13,18,38 Finally, 6 mutations identified in patients from this study had been previously reported: D303N (P8), T438M (P14) in 3 different families with MWS 18 and in 1 sporadic occurrence of CINCA syndrome, 39 F309S (P17) in 1 patient with CINCA/NOMID syndrome of severe phenotype, 13 and Y570C in 3 patients (P10, P16, P19) 2 other patients with severe CINCA/NOMID syndrome 20,39 (Table 1). None of the mutations were found in controls, as in patients' parents, when tested (Table 1).…”

“…One patient with the D303N mutation was initially reported to have MWS, 18 but the clinical features of this patient were recently reported to be more consistent with CINCA syndrome. 38 This example highlights the limitations of such an 33 ; and RuvB (PDB 1hqc [chain A]). 40 Alignment was generated by threading and PSI-BLAST procedures and was carefully refined and extended using the sensitive hydrophobic cluster analysis (HCA) ("Patients and methods").…”

Mutations in NALP12 cause hereditary periodic fever syndromes

“…However, the patients also have distinguishing clinical manifestations: urticaria and sensorineural hearing loss were only observed in family 1, in whom acute-phase reactants were not elevated during crises, whereas aphthous ulcers and lymphadenopathy were noticed in patient II.2 from family 2. Such interfamilial phenotypic heterogeneity is frequently observed in HPFs (19,20,(25)(26)(27); in this regard, it has even been shown that a same mutation (in NALP3) can be associated with different CAPSs (8,27,28). Furthermore, phenotypic heterogeneity also has been shown to be intrafamilial in this pathology, especially in NALP3-associated disorders (8-10).…”

Phenotype, Genotype, and Sustained Response to Anakinra in 22 Patients With Autoinflammatory Disease Associated With CIAS-1/NALP3 Mutations

“…5 It is apparent that FCAS, MWS, and NOMID represent a spectrum of disease intensity with overlapping features. 6,7 The NALP3 gene (also known as CIAS1) is expressed in peripheral blood leukocytes 8 and chondrocytes. 9 The NALP proteins are members of the death domain superfamily, and their nomenclature derives from their several motifs.…”