Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort
Abstract Purpose This study aimed to elucidate the reliability of clinical impressions based on ocular manifestations in patients suspected of heritable connective tissue disorders (HCTDs) compared to the final genetic diagnosis. Furthermore, it sought to determine the optimal diagnostic strategy fo...
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| Format: | Article |
| Language: | English |
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BMC
2025-04-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-025-00749-2 |
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| author | Qin-Meng Shu Yu-Qiao Ju Yuan Zong Ting Zhang Xin Huang Feng-juan Gao Qing Chang |
| author_facet | Qin-Meng Shu Yu-Qiao Ju Yuan Zong Ting Zhang Xin Huang Feng-juan Gao Qing Chang |
| author_sort | Qin-Meng Shu |
| collection | DOAJ |
| description | Abstract Purpose This study aimed to elucidate the reliability of clinical impressions based on ocular manifestations in patients suspected of heritable connective tissue disorders (HCTDs) compared to the final genetic diagnosis. Furthermore, it sought to determine the optimal diagnostic strategy for patients with HCTDs through pathogenicity analysis. Methods Clinical characteristics of 58 patients suspected of HCTDs were analyzed to establish provisional clinical diagnoses. Subsequently, next-generation sequence and Sanger sequence was performed to obtain genetic diagnoses. Pathogenicity of identified variants was assessed through conservation analysis and the functional impact, which was predicted using three-dimensional protein structure modeling. Results The provisional clinical diagnosis was concordant with the molecular diagnostic result in only 21 patients. Independent of the initial clinical impression, a probable genetic diagnosis was achieved for all 58 patients following comprehensive re-analysis of next-generation sequence data, combined with pathogenicity assessment using three-dimensional protein structure and conservation analysis of suspicious positive variants. Conclusion This study broadens the mutational spectrum of HCTDs with 31 novel variants. By employing innovative methodologies to delineate phenotype–genotype relationships, including the detection of potentially pathogenic variants, this work may inform future diagnostic strategies and guide comprehensive disease and organ system monitoring. Ongoing refinement and vigilant clinical oversight remain essential for patients and their families. |
| format | Article |
| id | doaj-art-9b7e5a3891ee44f282220fa15de9d28f |
| institution | OA Journals |
| issn | 1479-7364 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj-art-9b7e5a3891ee44f282220fa15de9d28f2025-08-20T02:17:10ZengBMCHuman Genomics1479-73642025-04-0119111810.1186/s40246-025-00749-2Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohortQin-Meng Shu0Yu-Qiao Ju1Yuan Zong2Ting Zhang3Xin Huang4Feng-juan Gao5Qing Chang6Eye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityAbstract Purpose This study aimed to elucidate the reliability of clinical impressions based on ocular manifestations in patients suspected of heritable connective tissue disorders (HCTDs) compared to the final genetic diagnosis. Furthermore, it sought to determine the optimal diagnostic strategy for patients with HCTDs through pathogenicity analysis. Methods Clinical characteristics of 58 patients suspected of HCTDs were analyzed to establish provisional clinical diagnoses. Subsequently, next-generation sequence and Sanger sequence was performed to obtain genetic diagnoses. Pathogenicity of identified variants was assessed through conservation analysis and the functional impact, which was predicted using three-dimensional protein structure modeling. Results The provisional clinical diagnosis was concordant with the molecular diagnostic result in only 21 patients. Independent of the initial clinical impression, a probable genetic diagnosis was achieved for all 58 patients following comprehensive re-analysis of next-generation sequence data, combined with pathogenicity assessment using three-dimensional protein structure and conservation analysis of suspicious positive variants. Conclusion This study broadens the mutational spectrum of HCTDs with 31 novel variants. By employing innovative methodologies to delineate phenotype–genotype relationships, including the detection of potentially pathogenic variants, this work may inform future diagnostic strategies and guide comprehensive disease and organ system monitoring. Ongoing refinement and vigilant clinical oversight remain essential for patients and their families.https://doi.org/10.1186/s40246-025-00749-2Heritable connective tissue disordersGenetic diagnosisStickler syndromeKnobloch syndromeWagner syndromeSevere myopia |
| spellingShingle | Qin-Meng Shu Yu-Qiao Ju Yuan Zong Ting Zhang Xin Huang Feng-juan Gao Qing Chang Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort Human Genomics Heritable connective tissue disorders Genetic diagnosis Stickler syndrome Knobloch syndrome Wagner syndrome Severe myopia |
| title | Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort |
| title_full | Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort |
| title_fullStr | Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort |
| title_full_unstemmed | Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort |
| title_short | Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort |
| title_sort | reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large chinese cohort |
| topic | Heritable connective tissue disorders Genetic diagnosis Stickler syndrome Knobloch syndrome Wagner syndrome Severe myopia |
| url | https://doi.org/10.1186/s40246-025-00749-2 |
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