The clinical phenotype and genotype of NLRP12-autoinflammatory disease: a Chinese case series with literature review
- PDF / 543,455 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 10 Downloads / 255 Views
ORIGINAL ARTICLE
The clinical phenotype and genotype of NLRP12‑autoinflammatory disease: a Chinese case series with literature review Wei Wang1 · Yu Zhou1,2 · Lin‑Qing Zhong1 · Zhuo Li1 · Shan Jian1 · Xiao‑Yan Tang1 · Hong‑Mei Song1 Received: 2 May 2019 / Accepted: 12 July 2019 © Children’s Hospital, Zhejiang University School of Medicine 2019
Abstract Background The nucleotide-binding oligomerization domain-like receptor protein 12 (NLRP12)-autoinflammatory disorder (NLRP12-AD) is a rare autoinflammatory disease characterized by recurrent fever, rash as well as musculoskeletal symptoms, which is rarely reported in Asian populations. Methods Three cases of NLRP12-AD presented to our hospital were studied after parental consents were obtained. Clinical presentations were recorded on a standardized case report form. Mutations of NLRP12 were detected by primary immunodeficiency disease panels and further examined by Sanger sequencing. PubMed literature search for relevant studies of systemic autoinflammatory disorders, especially NLRP12-AD between January, 2000 and January, 2019 was carried and the clinical data were summarized. Comparisons were made between groups in terms of onset age and of ethnicity. Results All our patients presented with fever, rash and arthritis/arthralgia, and sensorineural as well as sensorineural deafness (1/3), uveitis (1/3), abdominal pain (1/3), and myalgia (1/3). Two novel mutation variations, p.W581X and p.L558R, are reported here. In addition, we also found that two patients inherited the mutated alleles from their healthy parents, and this may be evidence of haploinsufficiency. Conclusions Although the genotypes are similar, the clinical manifestations between Chinese patients and Western patients vary thus highlighting the possible influence of ethnic and environmental factors. On the other hand, some genetic mutations may lead to specific phenotype, as we have found a high prevalence of sensorineural hearing loss among p.R284X patients. Keywords Autoinflammatory disease · NLRP12-AD · Recurrent fever
Introduction Many members of nucleotide-binding oligomerization domain-like receptor protein (NLR) family are important components of inflammasomes, including NLRP1, NLRP3, NLRC4, NLRP6, NLRP7, and NLRP12 [1]. Thus mutations in those genes may produce atypical inflammasomes and Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12519-019-00294-8) contains supplementary material, which is available to authorized users. * Hong‑Mei Song [email protected] 1
Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
School of Medicine, Tsinghua University, Beijing, China
2
cause inflammasomopathies, an important group in systemic autoinflammatory disorders (SAIDs). The NLRP12autoinflammatory disorder (NLRP12-AD), also called familial cold autoinflammatory syndrome 2 (FCAS 2), is such a disease caused by an autosomal dominant mutation of NLRP12 [2]. Like other disea
Data Loading...
