Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review

BACKGROUND: Some juvenile idiopathic arthritis (JIA) patients have a familial aggregation of the disease, and a few have been found to have a juvenile arthritis (JA) phenotype caused by a genetic mutation. JA due to LACC1 defects is a rare condition and it was never reported in China. METHODS: The clinical and molecular characteristics of a child with LACC1 gene mutation‐related juvenile arthritis, diagnosed by high‐throughput sequencing in Wuhan children's Hospital in 2021 were analyzed retrospectively; The literature and database were reviewed to summarize the clinical data and genotype characteristics of patients with JA caused by LACC1 gene mutation. RESULTS: Here, we report a 19‐month‐old Chinese male patient who presented with bilateral limb edema without a history of fever. Laboratory tests showed had moderate anemia and signs of inflammation: hemoglobin of 76 g/L, white blood cell count of 20.53 × 10(9), and platelet count of 1194 × 10(9); MRI showed the patient had synovitis and tenosynovitis in bilateral hands and wrists. Whole‐exome sequencing (WES) detected compound heterozygous variants, novel c.446_449dupTAAA and c.889T>C, in the LACC1 gene. Of the 52 patients reported in the literature (including this case), 38.9% had clinical symptoms of systemic juvenile idiopathic arthritis (sJIA), which tended to be caused by loss‐of‐function (LOF) mutation. Findings in this study expanded the spectrum of pathogenic variants and reveal the phenotypic heterogeneity of LACC1‐JA. CONCLUSIONS: Our study reported a rare case of juvenile arthritis, which is due to the compound heterozygous mutation of LACC1, including a new novel frameshift mutation c.446_449dupTAAA, and LACC1 C297R variant causes disease by potentially modifying the local conformation of proteins. The clinical and genetic findings in our study show that LACC1‐JA is highly heterogeneous, and gene testing is required for juvenile arthritis patients with a high inflammatory response at a young onset age.