The clinical phenotype and genotype of NLRP12-autoinflammatory disease: a Chinese case series with literature review

World J Pediatr. 2020 Oct;16(5):514-519. doi: 10.1007/s12519-019-00294-8. Epub 2019 Dec 9.


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.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child, Preschool
  • China
  • Female
  • Genotype
  • Hereditary Autoinflammatory Diseases / genetics*
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Phenotype


  • Intracellular Signaling Peptides and Proteins
  • NLRP12 protein, human