Clinical and genetic spectrum of 14 cases of NLRP3-associated autoinflammatory disease (NLRP3-AID) in China and a review of the literature

Yu Zhou; Wei Wang; Linqing Zhong; Lin Wang; Mingsheng Ma; Xiaoyan Tang; Zhuo Li; Changyan Wang; Lijuan Gou; Tiannan Zhang; Hongmei Song

doi:10.1186/s13023-022-02364-z

Clinical and genetic spectrum of 14 cases of NLRP3-associated autoinflammatory disease (NLRP3-AID) in China and a review of the literature

Orphanet J Rare Dis. 2022 Jun 6;17(1):214. doi: 10.1186/s13023-022-02364-z.

Authors

Yu Zhou^#^{1

2}, Wei Wang^#^{3

4}, Linqing Zhong^{1

2}, Lin Wang^{1

2}, Mingsheng Ma^{1

2}, Xiaoyan Tang^{1

2}, Zhuo Li^{1

2}, Changyan Wang^{1

2}, Lijuan Gou^{1

2}, Tiannan Zhang^{1

2}, Hongmei Song^{5

6}

Affiliations

¹ Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
² State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China.
³ Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. wangwei.a@163.com.
⁴ State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China. wangwei.a@163.com.
⁵ Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. songhm1021@126.com.
⁶ State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China. songhm1021@126.com.

^# Contributed equally.

Abstract

Background: NLRP3-associated autoinflammatory disease (NLRP3-AID), caused by mutations of NLRP3, is one of the autoinflammatory diseases affecting inflammasomes. Since there are little cases of Chinese NLRP3-AID, we reported 14 Chinese NLRP3-AID patients in our center and summarized the clinical features of all Chinese patients by reviewing the literature.

Results: Fourteen patients had been diagnosed as NLRP3-AID in our center. 12 different NLRP3 variants were identified, among which one is novel: p.Leu361Trp. Rash, recurrent fever, arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS), and increased inflammatory markers (including CRP, ESR, except Ferritin) were the common findings in Chinese patients. The frequencies of fever, neurological symptoms, musculoskeletal manifestations and ocular manifestations in Chinese patients might differ from that of patients from other regions. Besides, we also found clubbing fingers and optic neuritis in some NLRP3-AID patients, which were not commonly mentioned in previous reports.

Conclusion: In our study, we expanded the clinical spectrum as well as the genetic pathogenic variants of NLRP3-AID. We also found that there were some differences between Chinese patients and patients from other regions, and that Chinese patients were more likely to develop severe symptoms.

Keywords: Autoinflammatory disease; Inflammasomopathies; NLRP3; NLRP3-AID.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Asian People / genetics
Fever
Hereditary Autoinflammatory Diseases* / diagnosis
Hereditary Autoinflammatory Diseases* / genetics
Humans
Inflammasomes / genetics
Mutation / genetics
NLR Family, Pyrin Domain-Containing 3 Protein* / genetics

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein