Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review
Abstract Background Some juvenile idiopathic arthritis (JIA) patients have a familial aggregation of the disease, and a few have been found to have a juvenile arthritis (JA) phenotype caused by a genetic mutation. JA due to LACC1 defects is a rare condition and it was never reported in China. Method...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-07-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.2175 |
| _version_ | 1797782483071139840 |
|---|---|
| author | Yali Wu Shasha Wang Wen Yin Wei Yin Yan Ding |
| author_facet | Yali Wu Shasha Wang Wen Yin Wei Yin Yan Ding |
| author_sort | Yali Wu |
| collection | DOAJ |
| description | Abstract Background Some juvenile idiopathic arthritis (JIA) patients have a familial aggregation of the disease, and a few have been found to have a juvenile arthritis (JA) phenotype caused by a genetic mutation. JA due to LACC1 defects is a rare condition and it was never reported in China. Methods The clinical and molecular characteristics of a child with LACC1 gene mutation‐related juvenile arthritis, diagnosed by high‐throughput sequencing in Wuhan children's Hospital in 2021 were analyzed retrospectively; The literature and database were reviewed to summarize the clinical data and genotype characteristics of patients with JA caused by LACC1 gene mutation. Results Here, we report a 19‐month‐old Chinese male patient who presented with bilateral limb edema without a history of fever. Laboratory tests showed had moderate anemia and signs of inflammation: hemoglobin of 76 g/L, white blood cell count of 20.53 × 109, and platelet count of 1194 × 109; MRI showed the patient had synovitis and tenosynovitis in bilateral hands and wrists. Whole‐exome sequencing (WES) detected compound heterozygous variants, novel c.446_449dupTAAA and c.889T>C, in the LACC1 gene. Of the 52 patients reported in the literature (including this case), 38.9% had clinical symptoms of systemic juvenile idiopathic arthritis (sJIA), which tended to be caused by loss‐of‐function (LOF) mutation. Findings in this study expanded the spectrum of pathogenic variants and reveal the phenotypic heterogeneity of LACC1‐JA. Conclusions Our study reported a rare case of juvenile arthritis, which is due to the compound heterozygous mutation of LACC1, including a new novel frameshift mutation c.446_449dupTAAA, and LACC1 C297R variant causes disease by potentially modifying the local conformation of proteins. The clinical and genetic findings in our study show that LACC1‐JA is highly heterogeneous, and gene testing is required for juvenile arthritis patients with a high inflammatory response at a young onset age. |
| first_indexed | 2024-03-13T00:11:35Z |
| format | Article |
| id | doaj.art-646200d6469d4d599fc7ecfbb32c8c16 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-13T00:11:35Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-646200d6469d4d599fc7ecfbb32c8c162023-07-12T11:50:09ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-07-01117n/an/a10.1002/mgg3.2175Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature reviewYali Wu0Shasha Wang1Wen Yin2Wei Yin3Yan Ding4Department of Rheumatology and Immunology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College Huazhong University of Science & Technology Wuhan ChinaDepartment of Rheumatology and Immunology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College Huazhong University of Science & Technology Wuhan ChinaDepartment of Rheumatology and Immunology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College Huazhong University of Science & Technology Wuhan ChinaDepartment of Rheumatology and Immunology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College Huazhong University of Science & Technology Wuhan ChinaDepartment of Rheumatology and Immunology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College Huazhong University of Science & Technology Wuhan ChinaAbstract Background Some juvenile idiopathic arthritis (JIA) patients have a familial aggregation of the disease, and a few have been found to have a juvenile arthritis (JA) phenotype caused by a genetic mutation. JA due to LACC1 defects is a rare condition and it was never reported in China. Methods The clinical and molecular characteristics of a child with LACC1 gene mutation‐related juvenile arthritis, diagnosed by high‐throughput sequencing in Wuhan children's Hospital in 2021 were analyzed retrospectively; The literature and database were reviewed to summarize the clinical data and genotype characteristics of patients with JA caused by LACC1 gene mutation. Results Here, we report a 19‐month‐old Chinese male patient who presented with bilateral limb edema without a history of fever. Laboratory tests showed had moderate anemia and signs of inflammation: hemoglobin of 76 g/L, white blood cell count of 20.53 × 109, and platelet count of 1194 × 109; MRI showed the patient had synovitis and tenosynovitis in bilateral hands and wrists. Whole‐exome sequencing (WES) detected compound heterozygous variants, novel c.446_449dupTAAA and c.889T>C, in the LACC1 gene. Of the 52 patients reported in the literature (including this case), 38.9% had clinical symptoms of systemic juvenile idiopathic arthritis (sJIA), which tended to be caused by loss‐of‐function (LOF) mutation. Findings in this study expanded the spectrum of pathogenic variants and reveal the phenotypic heterogeneity of LACC1‐JA. Conclusions Our study reported a rare case of juvenile arthritis, which is due to the compound heterozygous mutation of LACC1, including a new novel frameshift mutation c.446_449dupTAAA, and LACC1 C297R variant causes disease by potentially modifying the local conformation of proteins. The clinical and genetic findings in our study show that LACC1‐JA is highly heterogeneous, and gene testing is required for juvenile arthritis patients with a high inflammatory response at a young onset age.https://doi.org/10.1002/mgg3.2175gene mutationjuvenile arthritisjuvenile idiopathic arthritisLACC1whole‐exome sequencing |
| spellingShingle | Yali Wu Shasha Wang Wen Yin Wei Yin Yan Ding Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review Molecular Genetics & Genomic Medicine gene mutation juvenile arthritis juvenile idiopathic arthritis LACC1 whole‐exome sequencing |
| title | Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review |
| title_full | Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review |
| title_fullStr | Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review |
| title_full_unstemmed | Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review |
| title_short | Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review |
| title_sort | clinical characteristics and genotype analysis of a chinese patient with juvenile arthritis due to novel lacc1 frameshift mutation and literature review |
| topic | gene mutation juvenile arthritis juvenile idiopathic arthritis LACC1 whole‐exome sequencing |
| url | https://doi.org/10.1002/mgg3.2175 |
| work_keys_str_mv | AT yaliwu clinicalcharacteristicsandgenotypeanalysisofachinesepatientwithjuvenilearthritisduetonovellacc1frameshiftmutationandliteraturereview AT shashawang clinicalcharacteristicsandgenotypeanalysisofachinesepatientwithjuvenilearthritisduetonovellacc1frameshiftmutationandliteraturereview AT wenyin clinicalcharacteristicsandgenotypeanalysisofachinesepatientwithjuvenilearthritisduetonovellacc1frameshiftmutationandliteraturereview AT weiyin clinicalcharacteristicsandgenotypeanalysisofachinesepatientwithjuvenilearthritisduetonovellacc1frameshiftmutationandliteraturereview AT yanding clinicalcharacteristicsandgenotypeanalysisofachinesepatientwithjuvenilearthritisduetonovellacc1frameshiftmutationandliteraturereview |