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Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus
BACKGROUND: Systemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375402/ https://www.ncbi.nlm.nih.gov/pubmed/35964089 http://dx.doi.org/10.1186/s12969-022-00722-6 |
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author | Lee, Wan-Fang Fan, Wen-Lang Tseng, Min-Hua Yang, Huang-Yu Huang, Jing-Long Wu, Chao-Yi |
author_facet | Lee, Wan-Fang Fan, Wen-Lang Tseng, Min-Hua Yang, Huang-Yu Huang, Jing-Long Wu, Chao-Yi |
author_sort | Lee, Wan-Fang |
collection | PubMed |
description | BACKGROUND: Systemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in patients fulfilling 2012 SLICC SLE classification criteria before the age of 5. CASE PRESENTATION: Among the 184 childhood-onset SLE patients regularly followed in a tertiary medical center in Taiwan, 7 cases (3.8%) of which onset ≦ 5 years of age were identified for characteristic review and genetic analysis. Compared to those onset at elder age, cases onset before the age of 5 are more likely to suffer from proliferative glomerulonephritis, renal thrombotic microangiopathy, neuropsychiatric disorder and failure to thrive. Causative genetic etiologies were identified in 3. In addition to the abundance of autoantibodies, patient with homozygous TREX1 (c.292_293 ins A) mutation presented with chilblain-like skin lesions, peripheral spasticity, endocrinopathy and experienced multiple invasive infections. Patient with SLC7A7 (c.625 + 1 G > A) mutation suffered from profound glomerulonephritis with full-house glomerular deposits as well as hyperammonemia, metabolic acidosis and episodic conscious disturbance. Two other cases harbored variants in lupus associating genes C1s, C2, DNASE1 and DNASE1L3 and another with CFHR4. Despite fulfilling the classification criteria for lupus, many of the patients required treatments beyond conventional therapy. CONCLUSIONS: Genetic etiologies and lupus mimickers were found among a substantial proportion of patients suspected with early-onset SLE. Detail clinical evaluation and genetic testing are important for tailored care and personalized treatment. |
format | Online Article Text |
id | pubmed-9375402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93754022022-08-14 Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus Lee, Wan-Fang Fan, Wen-Lang Tseng, Min-Hua Yang, Huang-Yu Huang, Jing-Long Wu, Chao-Yi Pediatr Rheumatol Online J Case Report BACKGROUND: Systemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in patients fulfilling 2012 SLICC SLE classification criteria before the age of 5. CASE PRESENTATION: Among the 184 childhood-onset SLE patients regularly followed in a tertiary medical center in Taiwan, 7 cases (3.8%) of which onset ≦ 5 years of age were identified for characteristic review and genetic analysis. Compared to those onset at elder age, cases onset before the age of 5 are more likely to suffer from proliferative glomerulonephritis, renal thrombotic microangiopathy, neuropsychiatric disorder and failure to thrive. Causative genetic etiologies were identified in 3. In addition to the abundance of autoantibodies, patient with homozygous TREX1 (c.292_293 ins A) mutation presented with chilblain-like skin lesions, peripheral spasticity, endocrinopathy and experienced multiple invasive infections. Patient with SLC7A7 (c.625 + 1 G > A) mutation suffered from profound glomerulonephritis with full-house glomerular deposits as well as hyperammonemia, metabolic acidosis and episodic conscious disturbance. Two other cases harbored variants in lupus associating genes C1s, C2, DNASE1 and DNASE1L3 and another with CFHR4. Despite fulfilling the classification criteria for lupus, many of the patients required treatments beyond conventional therapy. CONCLUSIONS: Genetic etiologies and lupus mimickers were found among a substantial proportion of patients suspected with early-onset SLE. Detail clinical evaluation and genetic testing are important for tailored care and personalized treatment. BioMed Central 2022-08-13 /pmc/articles/PMC9375402/ /pubmed/35964089 http://dx.doi.org/10.1186/s12969-022-00722-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Case Report Lee, Wan-Fang Fan, Wen-Lang Tseng, Min-Hua Yang, Huang-Yu Huang, Jing-Long Wu, Chao-Yi Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus |
title | Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus |
title_full | Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus |
title_fullStr | Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus |
title_full_unstemmed | Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus |
title_short | Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus |
title_sort | characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375402/ https://www.ncbi.nlm.nih.gov/pubmed/35964089 http://dx.doi.org/10.1186/s12969-022-00722-6 |
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