A novel TGFBR2 mutation causes Loeys-Dietz syndrome in a Chinese infant: A case report
Introduction: Loeys‐Dietz syndrome (LDS) is a rare autosomal dominant disorder with extensive connective tissue involvement. The diagnosis of this disease is mainly based on clinical features combined with the detection of pathogenic gene mutations, mainly mutations in the transforming growth factor...
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Elsevier
2025-01-01
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| author | Xin Liu Kaiqing Liu Lifu Hu Zixiao Liu Xinhua Liu Jiantao Wang |
| author_facet | Xin Liu Kaiqing Liu Lifu Hu Zixiao Liu Xinhua Liu Jiantao Wang |
| author_sort | Xin Liu |
| collection | DOAJ |
| description | Introduction: Loeys‐Dietz syndrome (LDS) is a rare autosomal dominant disorder with extensive connective tissue involvement. The diagnosis of this disease is mainly based on clinical features combined with the detection of pathogenic gene mutations, mainly mutations in the transforming growth factor-beta (TGF-β) signaling pathway. Methods: The molecular pathogenesis of a LDS syndrome proband and his family members was analyzed using whole exome sequencing and validated using Sanger sequencing. Molecular dynamics simulations and in vitro cell experiments further analyzed the structural changes and functional abnormalities of the variation. Results: This study describes the case of a 6-month-old infant diagnosed with LDS with typical craniofacial abnormalities, developmental delay, and a dilated aortic sinus (19 mm; Z-score 3.5). Genetic analysis showed the patient carried a novel de novo TGF-β receptor 2 (TGFBR2) mutation (NM_003242: c.1005_1007delGTA (p.Glu335_Tyr336delinsAsp)). Molecular dynamics simulation showed that the TGFBR2 c.1005_1007delGTA mutation changed the protein conformation, making the protein conformation more stable. The p.Glu335_Tyr336delinsAsp mutation significantly reduced TGF-β-induced gene transcription and phosphorylation of SMAD Family Member 2 (SMAD2) in vitro. Conclusions: Our comprehensive genetic analysis suggested that the p.Glu335_Tyr336delinsAsp variant of TGFBR2 caused aberrant TGF-β signaling and contributed to LDS in the patient. |
| format | Article |
| id | doaj-art-c95d3765ceef4bb4a06c552e61b66bee |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| spelling | doaj-art-c95d3765ceef4bb4a06c552e61b66bee2025-02-02T05:29:00ZengElsevierHeliyon2405-84402025-01-01112e42116A novel TGFBR2 mutation causes Loeys-Dietz syndrome in a Chinese infant: A case reportXin Liu0Kaiqing Liu1Lifu Hu2Zixiao Liu3Xinhua Liu4Jiantao Wang5Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, ChinaShenzhen Luohu Hospital Group, The Third Affiliated Hospital of Shenzhen University, Shenzhen, ChinaDepartment of Clinical Medicine, Shantou University Medical College, Shantou, ChinaShenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, ChinaShenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China; Corresponding author. Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, Guangdong, China.Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China; Corresponding author. Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, Guangdong, China.Introduction: Loeys‐Dietz syndrome (LDS) is a rare autosomal dominant disorder with extensive connective tissue involvement. The diagnosis of this disease is mainly based on clinical features combined with the detection of pathogenic gene mutations, mainly mutations in the transforming growth factor-beta (TGF-β) signaling pathway. Methods: The molecular pathogenesis of a LDS syndrome proband and his family members was analyzed using whole exome sequencing and validated using Sanger sequencing. Molecular dynamics simulations and in vitro cell experiments further analyzed the structural changes and functional abnormalities of the variation. Results: This study describes the case of a 6-month-old infant diagnosed with LDS with typical craniofacial abnormalities, developmental delay, and a dilated aortic sinus (19 mm; Z-score 3.5). Genetic analysis showed the patient carried a novel de novo TGF-β receptor 2 (TGFBR2) mutation (NM_003242: c.1005_1007delGTA (p.Glu335_Tyr336delinsAsp)). Molecular dynamics simulation showed that the TGFBR2 c.1005_1007delGTA mutation changed the protein conformation, making the protein conformation more stable. The p.Glu335_Tyr336delinsAsp mutation significantly reduced TGF-β-induced gene transcription and phosphorylation of SMAD Family Member 2 (SMAD2) in vitro. Conclusions: Our comprehensive genetic analysis suggested that the p.Glu335_Tyr336delinsAsp variant of TGFBR2 caused aberrant TGF-β signaling and contributed to LDS in the patient.http://www.sciencedirect.com/science/article/pii/S2405844025004967Case reportLoeys‐Dietz syndromeTransforming growth factor-betaMolecular dynamics |
| spellingShingle | Xin Liu Kaiqing Liu Lifu Hu Zixiao Liu Xinhua Liu Jiantao Wang A novel TGFBR2 mutation causes Loeys-Dietz syndrome in a Chinese infant: A case report Heliyon Case report Loeys‐Dietz syndrome Transforming growth factor-beta Molecular dynamics |
| title | A novel TGFBR2 mutation causes Loeys-Dietz syndrome in a Chinese infant: A case report |
| title_full | A novel TGFBR2 mutation causes Loeys-Dietz syndrome in a Chinese infant: A case report |
| title_fullStr | A novel TGFBR2 mutation causes Loeys-Dietz syndrome in a Chinese infant: A case report |
| title_full_unstemmed | A novel TGFBR2 mutation causes Loeys-Dietz syndrome in a Chinese infant: A case report |
| title_short | A novel TGFBR2 mutation causes Loeys-Dietz syndrome in a Chinese infant: A case report |
| title_sort | novel tgfbr2 mutation causes loeys dietz syndrome in a chinese infant a case report |
| topic | Case report Loeys‐Dietz syndrome Transforming growth factor-beta Molecular dynamics |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025004967 |
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