Al-Mayouf Sulaiman M, Yateem Mada, Al-Dusery Haya, Monies Dorota, Wakil Salma, AlShiakh Manal, AlEnazi Abdullatif, Aladaileh Boshra, Alzyoud Raed, Meyer Brian
Department of Pediatric Rheumatology, Riyadh, Saudi Arabia.
King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Int J Pediatr Adolesc Med. 2021 Mar;8(1):44-47. doi: 10.1016/j.ijpam.2020.11.005. Epub 2020 Nov 12.
The classification and pathogenic basis of juvenile idiopathic arthritis (JIA) are a subject of some controversy. Essentially, JIA is an exclusion diagnosis that represents a phenotypically heterogeneous group of arthritis of unknown origin. Familial aggregation of JIA supports the concept of genetic influence in the pathogenesis of JIA.
To present the spectrum of laccase domain-containing 1 (LACC1)-associated juvenile arthritis with clinical, biochemical, and molecular genetic data of a cohort of 43 patients, including 11 previously unpublished cases.
We studied 11 patients with different categories of juvenile idiopathic arthritis from 5 consanguineous families, all from Saudi Arabia, except 2 patients who were of Jordanian ethnicity. Whole-exome sequencing was used to identify the disease-causing variant of LACC1. We also reviewed the clinical spectrum and molecular genetic data of previously published cases of LACC1-associated juvenile arthritis.
This study describes 43 (29 females, 14 males) patients from consanguineous multiplex families. Most of the included patients were of Arab origin with 86% having early onset disease. The most frequent categories were systemic (19 patients) and rheumatoid factor-negative polyarticular (19 patients). Thirty-seven (86%) had progressive erosive arthritis and 10 (23.3%) had persistent limb lymphedema. None of the patients had features of macrophage activation syndrome. Genetic analysis confirmed LACC1 variant in all patients; 22 patients had common founder mutation (LACC1: c.850T > C,p.C284R), while the others showed different LACC1 variants. All patients were treated aggressively with methotrexate and sequential biologic agents. Most of them showed a poor response to treatment.
This report expands the pathogenic variants of LACC1 and the clinical spectrum associated with this genetic subset of juvenile arthritis. The predominance of autosomal-recessive inheritance and strong genetic evidence allowed us to propose LACC1-associated juvenile arthritis as a distinct disorder.
青少年特发性关节炎（JIA）的分类及发病机制存在一定争议。本质上，JIA是一种排除性诊断，代表一组病因不明、表型各异的关节炎。JIA的家族聚集现象支持遗传因素在其发病机制中起作用的观点。
通过43例患者（包括11例此前未发表的病例）的临床、生化及分子遗传学数据，展示含漆酶结构域蛋白1（LACC1）相关青少年关节炎的谱系。
我们研究了来自5个沙特阿拉伯近亲家庭的11例不同类型青少年特发性关节炎患者，其中2例为约旦裔。采用全外显子测序确定LACC1的致病变异。我们还回顾了此前发表的LACC1相关青少年关节炎病例的临床谱系及分子遗传学数据。
本研究描述了来自近亲多病例家庭的43例患者（29例女性，14例男性）。纳入的患者大多为阿拉伯裔，86%为早发型疾病。最常见的类型是全身型（19例）和类风湿因子阴性多关节型（19例）。37例（86%）有进行性侵蚀性关节炎，10例（23.3%）有持续性肢体淋巴水肿。所有患者均无巨噬细胞活化综合征特征。基因分析证实所有患者均存在LACC1变异；22例患者有共同的始祖突变（LACC1：c.850T>C，p.C284R），其余患者表现为不同的LACC1变异。所有患者均接受了甲氨蝶呤及序贯生物制剂的积极治疗。大多数患者对治疗反应不佳。
本报告扩展了LACC1的致病变异及与此遗传亚型青少年关节炎相关的临床谱系。常染色体隐性遗传的优势及有力的遗传学证据使我们能够将LACC1相关青少年关节炎作为一种独特的疾病提出。
