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The phenotype and genotype of Chinese adult patients with NLRP3-associated autoinflammatory disease

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Abstract

Objectives

NLRP3-associated autoinflammatory disease (NLRP3-AID) is a spectrum of autosomal dominant inherited diseases associated with NLRP3 gene mutations. Reports of Chinese NLRP3-AID cases are limited to date. In the present study, we aim to describe the phenotype and genotype of a cohort of Chinese adult NLRP3-AID patients

Methods

This single-center study included sixteen adult patients diagnosed with NLRP3-AID at Department of Rheumatology, Peking Union Medical College Hospital from April 2015 to September 2021. Whole-exome sequencing using next-generation sequencing was performed in each patient. Clinical data and mutational information were compared with a European cohort.

Results

The median age of disease onset was 16 (0–46) years old, and adult-onset was observed in 4 patients (25%). The median time of diagnosis delay was 20 (0–39) years. Five patients (31.3%) had family history of similar symptoms. The most common clinical manifestations were recurrent fever (93.8%), arthralgia/arthritis (81.3%), skin rash (75%), myalgia (62.5%), and central nervous system manifestations (50%). Heterozygous NLRP3 variants detected in these patients were p.T348M (n = 4, 25%), Q703K, V70M, K129R, M116I, P38S, V442I, D303G, G326E, A439V, K829T, L632F and V198M (n = 1, separately). All the variants were missense mutations.

Conclusions

We reported the largest case series of Chinese adult NLRP3-AID patients. The distinct symptoms of NLRP3-AID patients suggest the heterogeneity of disease. P38S, M116I, K129R, V442I and K829T were identified as novel NLRP3 variants. These data expand the clinical phenotypic and genotypic profiles of NLRP3-AID.

Key Points

• We characterized the clinical and genetic features of sixteen Chinese adult NLRP3-AID patients.

• Thirteen NLRP3 gene variants were confirmed in this cohort, and P38S, M116I, K129R, V442I and K829T were identified as novel variants.

• Clinical data and mutation information were compared with a European cohort.

• We hope these data would expand the phenotypic and genotypic profile of NLRP3-AID and raise the awareness of early diagnosis and accurate treatment among rheumatologists.

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Data availability

The original data presented in the study are included in this article. Further inquiries can be directed to the corresponding author.

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Acknowledgements

We would like to acknowledge all the patients for their consents to participate in the study.

Funding

This work was supported by the Natural Science Foundation of Beijing (Grant No.7192170); the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (Grant No.2017-I2M-3–001); the National Key Research and Development Program of China (Grant No.2016YFC0901500; 2016YFC0901501); and the National High Level Hospital Clinical Research Funding (Grant No.2022-PUMCH-D-002; 2022-PUMCH-B-013).

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Author notes

  1. Na Wu, Di Wu and Junke Miao contributed equally to the work.

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China

    Na Wu, Di Wu, Junke Miao, Mengzhu Zhao & Min Shen

  2. Department of Otolaryngological, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Yi Wang

  3. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Weihong Yu

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  1. Na Wu
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Correspondence to Min Shen.

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Wu, N., Wu, D., Miao, J. et al. The phenotype and genotype of Chinese adult patients with NLRP3-associated autoinflammatory disease. Clin Rheumatol 42, 2841–2848 (2023). https://doi.org/10.1007/s10067-023-06679-5

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  • DOI: https://doi.org/10.1007/s10067-023-06679-5

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