Pitfalls in the diagnosis of apparent homozygous mutations: two cases of IL10RA deficiency inflammatory bowel disease and a literature review
Abstract Background In East Asia, IL10RA is the predominant pathogenic gene in patients with very early-onset inflammatory bowel disease (VEO-IBD), frequently characterised by refractory diarrhoea and severe perianal disease, resulting in elevated death rates. IL10RA-deficient IBD, an autosomal rece...
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BMC
2025-07-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03779-0 |
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| author | Xiu Shi Ziqing Ye Lai Qian Wenhui Hu Ye Yang Chunmeng He Zhiheng Huang Bingbing Wu Ying Huang |
| author_facet | Xiu Shi Ziqing Ye Lai Qian Wenhui Hu Ye Yang Chunmeng He Zhiheng Huang Bingbing Wu Ying Huang |
| author_sort | Xiu Shi |
| collection | DOAJ |
| description | Abstract Background In East Asia, IL10RA is the predominant pathogenic gene in patients with very early-onset inflammatory bowel disease (VEO-IBD), frequently characterised by refractory diarrhoea and severe perianal disease, resulting in elevated death rates. IL10RA-deficient IBD, an autosomal recessive genetic disorder, has been documented to be inherited through the conventional compound heterozygous or homozygous mutation patterns from both parents. We present two cases with apparent homozygosity resulting from distinct causes, both of which seem homozygous on the genetic map. Further investigation reveals that detecting hidden genetic patterns is essential for accurate diagnosis, genetic counselling, and disease mechanism analysis. Methods Peripheral blood samples were collected from two patients and their parents. Whole-exome sequencing (WES), Sanger sequencing, Comparative genomic hybridisation (CGH) and SNP array, Capture-based CNV (CapCNV) analysis, and real-time quantitative PCR (qPCR) were employed to investigate the genetic mechanisms and variants within the families. Both patients were followed up, and descriptive analyses were performed to characterise their clinical phenotypes, biochemical parameters, endoscopic findings, and intestinal histopathology. Multiple databases were systematically searched to review all cases of IBD with large IL10RA deletions. Results Two families underwent WES, and a homozygous mutation was identified in the IL10RA gene on chromosome 11 in both families. In patient 1, pedigree analysis, CGH and SNP 4 × 180 K microarray testing identified paternal uniparental diploidy (c.301C > T/11q12.3-11q25del) [upd (11) pat] on chromosome 11. Patient 2 had compound heterozygosity (c. 299 T > G/exon2_3del), comprising a point mutation and an overlapping exon deletion mutation in IL10RA, as determined using familial analysis, Sanger sequencing, CapCNV analysis, and qPCR validation. In addition, the study systematically reviewed 15 cases of IBD patients with large deletions in the IL10RA gene from the literature. Conclusions This is the first description of two cases of apparent homozygosity in IL10RA. This report emphasizes the importance of optimizing the genetic analysis workflow, especially when there is doubt about the initial whole exome sequencing results. |
| format | Article |
| id | doaj-art-d0a0f00f4f7a4f2f982c91d6266b7f13 |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-d0a0f00f4f7a4f2f982c91d6266b7f132025-08-20T03:45:32ZengBMCOrphanet Journal of Rare Diseases1750-11722025-07-012011810.1186/s13023-025-03779-0Pitfalls in the diagnosis of apparent homozygous mutations: two cases of IL10RA deficiency inflammatory bowel disease and a literature reviewXiu Shi0Ziqing Ye1Lai Qian2Wenhui Hu3Ye Yang4Chunmeng He5Zhiheng Huang6Bingbing Wu7Ying Huang8Department of Gastroenterology, Children’s Hospital of Fudan UniversityDepartment of Gastroenterology, Children’s Hospital of Fudan UniversityDepartment of Gastroenterology, Children’s Hospital of Fudan UniversityDepartment of Gastroenterology, Children’s Hospital of Fudan UniversityDepartment of Gastroenterology, Children’s Hospital of Fudan UniversityDepartment of Gastroenterology, Children’s Hospital of Fudan UniversityDepartment of Gastroenterology, Children’s Hospital of Fudan UniversityKey Laboratory of Birth Defects, Children’s Hospital of Fudan UniversityDepartment of Gastroenterology, Children’s Hospital of Fudan UniversityAbstract Background In East Asia, IL10RA is the predominant pathogenic gene in patients with very early-onset inflammatory bowel disease (VEO-IBD), frequently characterised by refractory diarrhoea and severe perianal disease, resulting in elevated death rates. IL10RA-deficient IBD, an autosomal recessive genetic disorder, has been documented to be inherited through the conventional compound heterozygous or homozygous mutation patterns from both parents. We present two cases with apparent homozygosity resulting from distinct causes, both of which seem homozygous on the genetic map. Further investigation reveals that detecting hidden genetic patterns is essential for accurate diagnosis, genetic counselling, and disease mechanism analysis. Methods Peripheral blood samples were collected from two patients and their parents. Whole-exome sequencing (WES), Sanger sequencing, Comparative genomic hybridisation (CGH) and SNP array, Capture-based CNV (CapCNV) analysis, and real-time quantitative PCR (qPCR) were employed to investigate the genetic mechanisms and variants within the families. Both patients were followed up, and descriptive analyses were performed to characterise their clinical phenotypes, biochemical parameters, endoscopic findings, and intestinal histopathology. Multiple databases were systematically searched to review all cases of IBD with large IL10RA deletions. Results Two families underwent WES, and a homozygous mutation was identified in the IL10RA gene on chromosome 11 in both families. In patient 1, pedigree analysis, CGH and SNP 4 × 180 K microarray testing identified paternal uniparental diploidy (c.301C > T/11q12.3-11q25del) [upd (11) pat] on chromosome 11. Patient 2 had compound heterozygosity (c. 299 T > G/exon2_3del), comprising a point mutation and an overlapping exon deletion mutation in IL10RA, as determined using familial analysis, Sanger sequencing, CapCNV analysis, and qPCR validation. In addition, the study systematically reviewed 15 cases of IBD patients with large deletions in the IL10RA gene from the literature. Conclusions This is the first description of two cases of apparent homozygosity in IL10RA. This report emphasizes the importance of optimizing the genetic analysis workflow, especially when there is doubt about the initial whole exome sequencing results.https://doi.org/10.1186/s13023-025-03779-0IL10RAApparent homozygosityUniparental disomyGene deletion |
| spellingShingle | Xiu Shi Ziqing Ye Lai Qian Wenhui Hu Ye Yang Chunmeng He Zhiheng Huang Bingbing Wu Ying Huang Pitfalls in the diagnosis of apparent homozygous mutations: two cases of IL10RA deficiency inflammatory bowel disease and a literature review Orphanet Journal of Rare Diseases IL10RA Apparent homozygosity Uniparental disomy Gene deletion |
| title | Pitfalls in the diagnosis of apparent homozygous mutations: two cases of IL10RA deficiency inflammatory bowel disease and a literature review |
| title_full | Pitfalls in the diagnosis of apparent homozygous mutations: two cases of IL10RA deficiency inflammatory bowel disease and a literature review |
| title_fullStr | Pitfalls in the diagnosis of apparent homozygous mutations: two cases of IL10RA deficiency inflammatory bowel disease and a literature review |
| title_full_unstemmed | Pitfalls in the diagnosis of apparent homozygous mutations: two cases of IL10RA deficiency inflammatory bowel disease and a literature review |
| title_short | Pitfalls in the diagnosis of apparent homozygous mutations: two cases of IL10RA deficiency inflammatory bowel disease and a literature review |
| title_sort | pitfalls in the diagnosis of apparent homozygous mutations two cases of il10ra deficiency inflammatory bowel disease and a literature review |
| topic | IL10RA Apparent homozygosity Uniparental disomy Gene deletion |
| url | https://doi.org/10.1186/s13023-025-03779-0 |
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