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. 2021 Mar;8(1):44-47.
doi: 10.1016/j.ijpam.2020.11.005. Epub 2020 Nov 12.

New or vanishing frontiers: LACC1- associated juvenile arthritis

Sulaiman M Al-Mayouf  1   2 , Mada Yateem  1   2 , Haya Al-Dusery  2 , Dorota Monies  2 , Salma Wakil  2 , Manal AlShiakh  2 , Abdullatif AlEnazi  3 , Boshra Aladaileh  4 , Raed Alzyoud  4 , Brian Meyer  2
Affiliations

New or vanishing frontiers: LACC1- associated juvenile arthritis

Sulaiman M Al-Mayouf et al. Int J Pediatr Adolesc Med. 2021 Mar.

Abstract

Background: 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.

Objective: 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arthritis with clinical, biochemical, and molecular genetic data of a cohort of 43 patients, including 11 previously unpublished cases.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Arthropathy; Familial arthritis; Juvenile idiopathic arthritis; LACC1 associated juvenile arthritis.

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Conflict of interest statement

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome.We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication. We understand that the Corresponding Author is the sole contact for the Editorial process. He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs.

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