Interdepartmental Research Centre of Systemic Autoimmune and Autoinflammatory Diseases, Unit of Rheumatology, Policlinico Le Scotte, University of Siena, Siena, Italy.
Clin Exp Rheumatol. 2012 Nov-Dec;30(6):943-6. Epub 2012 Dec 17.
Cryopyrin-associated periodic syndromes (CAPS) comprise a spectrum of apparently distinct, rare, autosomal dominant autoinflammatory disorders of increasing severity caused by NLRP3 gene mutations. The Q703K allele is a variant of unknown pathogenetic significance, and has been considered to be both a clinically unremarkable polymorphism and a low- penetrance mutation.
To analyse the long-term clinical course in a cohort of patients presenting with periodic fever attacks and carrying the Q703K mutation in the NLRP3 gene.
Seven Caucasian patients (mean age 37.3±8.5 years, 2 males and 5 females) were identified as carriers of the Q703K mutation among 71 patients with CAPS-like symptoms.
The mean age at disease onset was 25.58±16.08 years and the mean disease duration was 12.28±8.36. The mean number of febrile episodes was 7.56±6.48 and the mean duration of fever attacks was 6.66±4.71 days. Six out of 7 patients had a low grade fever, while 1 patient had no fever episodes. All patients were characterised by symptoms consistent with recurrent inflammatory syndrome. Six patients out of 7 presented skin lesions, 4/7 arthralgia, 4/7 myalgia, 4/7 conjunctivitis, 3/7 headache. All patients also complained of severe fatigue. In 4/7 patients symptoms were triggered or worsened by generalised cold exposure.
We suggest that patients carrying the low-penetrance Q703K mutation in the NLRP3 gene may present with FCAS-like symptoms. However, given the high frequency of healthy carriers, the role of additional, still unknown genetic and/or environmental modifiers is conceivable.
冷吡啉相关周期性综合征 (CAPS) 是一组明显不同的、罕见的、常染色体显性自身炎症性疾病谱，由 NLRP3 基因突变引起，其严重程度逐渐增加。Q703K 等位基因是一种致病性意义不明的变体，被认为是一种临床无明显意义的多态性和低外显率突变。
分析一组以周期性发热发作为表现并携带 NLRP3 基因 Q703K 突变的患者的长期临床病程。
在 71 例具有 CAPS 样症状的患者中，鉴定出 7 例（平均年龄 37.3±8.5 岁，男性 2 例，女性 5 例）为 NLRP3 基因 Q703K 突变携带者。
疾病发病年龄的平均值为 25.58±16.08 岁，病程的平均值为 12.28±8.36 年。发热发作的平均次数为 7.56±6.48 次，发热发作的平均持续时间为 6.66±4.71 天。7 例患者中有 6 例有低热，1 例无发热发作。所有患者均表现为反复发作的炎症综合征症状。6 例患者有皮肤损伤，4 例有关节炎，4 例有肌痛，4 例有结膜炎，3 例有头痛。所有患者均主诉严重疲劳。4/7 例患者症状由全身寒冷暴露诱发或加重。
我们建议，携带 NLRP3 基因低外显率 Q703K 突变的患者可能表现为 FCAS 样症状。然而，鉴于健康携带者的高频率，尚不清楚的其他遗传和/或环境修饰因子的作用是可以想象的。
