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New or vanishing frontiers: LACC1-associated juvenile arthritis
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 conce...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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King Faisal Specialist Hospital and Research Centre
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922844/ https://www.ncbi.nlm.nih.gov/pubmed/33718577 http://dx.doi.org/10.1016/j.ijpam.2020.11.005 |
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author | Al-Mayouf, Sulaiman M. Yateem, Mada Al-Dusery, Haya Monies, Dorota Wakil, Salma AlShiakh, Manal AlEnazi, Abdullatif Aladaileh, Boshra Alzyoud, Raed Meyer, Brian |
author_facet | Al-Mayouf, Sulaiman M. Yateem, Mada Al-Dusery, Haya Monies, Dorota Wakil, Salma AlShiakh, Manal AlEnazi, Abdullatif Aladaileh, Boshra Alzyoud, Raed Meyer, Brian |
author_sort | Al-Mayouf, Sulaiman M. |
collection | PubMed |
description | 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arthritis with clinical, biochemical, and molecular genetic data of a cohort of 43 patients, including 11 previously unpublished cases.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. |
format | Online Article Text |
id | pubmed-7922844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | King Faisal Specialist Hospital and Research Centre |
record_format | MEDLINE/PubMed |
spelling | pubmed-79228442021-03-12 New or vanishing frontiers: LACC1-associated juvenile arthritis Al-Mayouf, Sulaiman M. Yateem, Mada Al-Dusery, Haya Monies, Dorota Wakil, Salma AlShiakh, Manal AlEnazi, Abdullatif Aladaileh, Boshra Alzyoud, Raed Meyer, Brian Int J Pediatr Adolesc Med Original Article 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. King Faisal Specialist Hospital and Research Centre 2021-03 2020-11-12 /pmc/articles/PMC7922844/ /pubmed/33718577 http://dx.doi.org/10.1016/j.ijpam.2020.11.005 Text en © 2020 Publishing services provided by Elsevier B.V. on behalf of King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Al-Mayouf, Sulaiman M. Yateem, Mada Al-Dusery, Haya Monies, Dorota Wakil, Salma AlShiakh, Manal AlEnazi, Abdullatif Aladaileh, Boshra Alzyoud, Raed Meyer, Brian New or vanishing frontiers: LACC1-associated juvenile arthritis |
title | New or vanishing frontiers: LACC1-associated juvenile arthritis |
title_full | New or vanishing frontiers: LACC1-associated juvenile arthritis |
title_fullStr | New or vanishing frontiers: LACC1-associated juvenile arthritis |
title_full_unstemmed | New or vanishing frontiers: LACC1-associated juvenile arthritis |
title_short | New or vanishing frontiers: LACC1-associated juvenile arthritis |
title_sort | new or vanishing frontiers: lacc1-associated juvenile arthritis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922844/ https://www.ncbi.nlm.nih.gov/pubmed/33718577 http://dx.doi.org/10.1016/j.ijpam.2020.11.005 |
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