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New or vanishing frontiers: LACC1-associated juvenile arthritis
- Source :
- International Journal of Pediatrics & Adolescent Medicine, International Journal of Pediatrics and Adolescent Medicine, Vol 8, Iss 1, Pp 44-47 (2021)
- Publication Year :
- 2020
- Publisher :
- King Faisal Specialist Hospital and Research Centre, 2020.
-
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arthritis with clinical, biochemical, and molecular genetic data of a cohort of 43 patients, including 11 previously unpublished cases.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.
- Subjects :
- medicine.medical_specialty
050402 sociology
Arthritis
Arthropathy
03 medical and health sciences
0302 clinical medicine
0504 sociology
030225 pediatrics
Internal medicine
medicine
Juvenile
Familial arthritis
business.industry
05 social sciences
lcsh:RJ1-570
Family aggregation
lcsh:Pediatrics
Juvenile idiopathic arthritis
medicine.disease
LACC1 associated juvenile arthritis
Lymphedema
Macrophage activation syndrome
Pediatrics, Perinatology and Child Health
Cohort
Methotrexate
Original Article
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 23526467
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- International Journal of Pediatrics & Adolescent Medicine
- Accession number :
- edsair.doi.dedup.....9304deab67f20f762b658159f26c6f9f