The 468th case: periodic fever, abdominal pain, small intestinal ulcers, NOD2 gene mutation / 中华内科杂志

Fever and abdominal pain are common symptoms and could be main manifestations in patients with autoinflammatory diseases.A 48-year-old female patient was admitted with recurrent fever and abdominal pain for 9 years.Serum level of inflammatory markers synchronously fluctuated with fever,and returned to normal when fever subsided.The periodic episodes of fever occurred every 1 to 4 months and failed to respond to empirical antibiotics.Whole exome sequencing showed heterozygous mutation of NOD2 gene q902k,leading to the final diagnosis of autoinflammatory disease.Corticosteroid and tripterygiumglycosides were effective for the disease remission.

A familial case of Blau syndrome caused by dual NOD2 genetic mutations / 中华实用儿科临床杂志

Objective To provide the diagnostic proof for a suspected Chinese family with BS,and NOD2 gene mutation types and clinical features were analyzed in this study.Methods Nine members (4 males and 5 females) of this family were enrolled.To clarify the genotype,the whole exome sequencing by next-generation sequencing from the proband and his parents was performed,and all members were subjected to Sanger sequencing.For the newly discovered NOD2 missense mutation,its pathological predictions were conducted online by adopting polyphen software.Clinical data of affected cases diagnosed by NOD2 analysis were collected to analyze illustrate the clinical features.Results (1)The proband of the family was a 5-year-old Chinese Han boy,who had the clinical triad of dermatitis,polyarthritis and uveitis.The body temperature and C-reactive protein (CRP) was normal.Besides the proband,2 members were diagnosed as BS by means of NOD2 analysis.The coexistence of 2 missense mutations was detected.One novel mutation was c.1981G ＞ C,p.A661 P,and another previously reported one was c.2006A ＞ G,p.H669A.(2) Mutations identified in the male proband were inherited from his father.Tracing the other pedigree members,it was disclosed that his grandmother had the heterozygous dual NOD2 mutations.The proband displayed a phenotype featuring the symptom triad of granulomatous dermatitis,symmetric arthritis,and recurrent uveitis,with normal temperature and CRP level.Conclusions The coexistence of A661P and H669A mutations in NOD2 caused BS in a Chinese pedigree,which derived from the proband's grandmother.This is the first report of A661P mutation in NOD2 in a Chinese pedigree of this disease.The proband has multi hydatoncus surrounding multi-joints,but no persistent fever and no elevated CRP,which may help to differentiate BS from other inherited autoinllammatory diseases in clinical settings.