Caroli F, Pontillo A, D'Osualdo A, Travan L, Ceccherini I, Crovella S, Alessio M, Stabile A, Gattorno M, Tommasini A, Martini A, Lepore L
Department of Molecular Genetics, IRCCS G. Gaslini, Genoa, Italy.
Rheumatology (Oxford). 2007 Mar;46(3):473-8. doi: 10.1093/rheumatology/kel269. Epub 2006 Aug 18.
We report the experience of the Italian Registry of patients affected by chronic infantile neurological, cutaneous, articular (CINCA) syndrome. The clinical and genetic features of 12 unrelated Italian patients with CINCA syndrome are described, focusing on the possible influence of the presence of CIAS1/cryopyrin mutations on the phenotype of the disease and on its prognosis.
The clinical features of 12 Italian CINCA patients were evaluated. Genomic DNA of the patients was sequenced using specific primers for CIAS1 and ASC genes.
Our patients shared typical CINCA characteristics and, sometimes, remarkable perinatal events, peculiar of CIAS1-mutated patients. Seven patients carried CIAS1 missense mutation, localized within the nucleotide binding domain of cryopyrin. Four previously described mutations and three new heterozygous CIAS1 missense mutations were identified. ASC gene, encoding for a direct interactor of cryopyrin, was not mutated in Italian CINCA patients. Finally, we reported the efficacy and safety of anti-IL1 therapy (Anakinra) in seven patients with a particularly severe CINCA phenotype.
Despite some common signs-used as syndrome hallmarks-we observed a high variability in symptoms, genetic results and outcomes in Italian CINCA patients. In contrast with other authors, we cannot find out any correlation between mutations in CIAS1 and CINCA severity, but we underlined the concomitance of perinatal events and mental retardation only in CIAS1 mutated subjects. Finally, we confirmed the efficacy of Anakinra treatment, both in CIAS1-mutated and non-mutated patients.
我们报告了意大利慢性婴儿神经、皮肤、关节（CINCA）综合征患者登记处的经验。描述了12例不相关的意大利CINCA综合征患者的临床和遗传特征，重点关注CIAS1/冷吡啉突变的存在对疾病表型及其预后的可能影响。
评估了12例意大利CINCA患者的临床特征。使用针对CIAS1和ASC基因的特异性引物对患者的基因组DNA进行测序。
我们的患者具有典型的CINCA特征，有时还有CIAS1突变患者特有的显著围产期事件。7例患者携带CIAS1错义突变，定位于冷吡啉的核苷酸结合域内。鉴定出4种先前描述的突变和3种新的杂合CIAS1错义突变。编码冷吡啉直接相互作用分子的ASC基因在意大利CINCA患者中未发生突变。最后，我们报告了抗IL-1治疗（阿那白滞素）对7例具有特别严重CINCA表型患者的疗效和安全性。
尽管有一些共同的体征作为综合征的标志，但我们观察到意大利CINCA患者在症状、遗传结果和预后方面存在高度变异性。与其他作者不同，我们未发现CIAS1突变与CINCA严重程度之间存在任何相关性，但我们强调围产期事件和智力迟钝仅在CIAS1突变的受试者中同时出现。最后，我们证实了阿那白滞素治疗对CIAS1突变和未突变患者均有效。
