TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutations
Abstract Background Tricho‐rhino‐phalangeal syndrome (TRPS) is a rare autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, a pear‐shaped nose, and cone‐shaped epiphyses. This condition is caused by hap...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1417 |
| _version_ | 1797300994329018368 |
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| author | Chen Wang Yufei Xu Yanrong Qing Ruen Yao Niu Li Xiumin Wang Tingting Yu Jian Wang |
| author_facet | Chen Wang Yufei Xu Yanrong Qing Ruen Yao Niu Li Xiumin Wang Tingting Yu Jian Wang |
| author_sort | Chen Wang |
| collection | DOAJ |
| description | Abstract Background Tricho‐rhino‐phalangeal syndrome (TRPS) is a rare autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, a pear‐shaped nose, and cone‐shaped epiphyses. This condition is caused by haploinsufficiency or dominant‐negative effect of the TRPS1 gene. Methods In this study, we analyzed the clinical and genetic data of five unrelated TRPS patients. They were suspected of having TRPS on the basis of clinical and radiological features including typical hair and facial features, as well as varying degrees of skeletal abnormalities. Next‐generation sequencing was performed to identify variants of the TRPS1 gene in the five patients. Results In patient 1, we found a novel mutation at c.1338C>A (p.Tyr446*) (de novo). Patient 2 had a novel phenotype of hydrocephaly and Arnold–Chiari syndrome and we also found a maternally inherited novel mutation at c.2657C>A (p.Ser886*). Patient 3 had a de novo novel mutation at c.2726G>C (p.Cys909Ser) leading to more severe phenotypes. Patient 4 had a paternally inherited known mutation at c.2762G>A (p.Arg921Gln). Patient 5 with a novel phenotype of hepatopathy had a novel deletion at [GRCh37] del(8)(q23.3‐q24.11) chr8:g.116,420,724‐119,124,058 (over 2,700 kb). In addition, the patient 3 who harboring missense variants in the GATA binding domain of TRPS1 showed more severe craniofacial and skeletal phenotypes. Conclusions We describe four novel mutations and two novel phenotypes in five patients. The mutational and phenotypic spectrum of TRPS is broadened by our study on TRPS mutations. Our results reveal the significance of molecular analysis of TRPS1 for improving the clinical diagnosis of TRPS. |
| first_indexed | 2024-03-07T23:15:03Z |
| format | Article |
| id | doaj.art-63a252b214c34318983068181cbaa2cb |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:15:03Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-63a252b214c34318983068181cbaa2cb2024-02-21T12:03:03ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-10-01810n/an/a10.1002/mgg3.1417TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutationsChen Wang0Yufei Xu1Yanrong Qing2Ruen Yao3Niu Li4Xiumin Wang5Tingting Yu6Jian Wang7Department of Medical Genetics and Molecular Diagnostic Laboratory Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of ChinaDepartment of Endocrinology and Metabolism Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of ChinaAbstract Background Tricho‐rhino‐phalangeal syndrome (TRPS) is a rare autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, a pear‐shaped nose, and cone‐shaped epiphyses. This condition is caused by haploinsufficiency or dominant‐negative effect of the TRPS1 gene. Methods In this study, we analyzed the clinical and genetic data of five unrelated TRPS patients. They were suspected of having TRPS on the basis of clinical and radiological features including typical hair and facial features, as well as varying degrees of skeletal abnormalities. Next‐generation sequencing was performed to identify variants of the TRPS1 gene in the five patients. Results In patient 1, we found a novel mutation at c.1338C>A (p.Tyr446*) (de novo). Patient 2 had a novel phenotype of hydrocephaly and Arnold–Chiari syndrome and we also found a maternally inherited novel mutation at c.2657C>A (p.Ser886*). Patient 3 had a de novo novel mutation at c.2726G>C (p.Cys909Ser) leading to more severe phenotypes. Patient 4 had a paternally inherited known mutation at c.2762G>A (p.Arg921Gln). Patient 5 with a novel phenotype of hepatopathy had a novel deletion at [GRCh37] del(8)(q23.3‐q24.11) chr8:g.116,420,724‐119,124,058 (over 2,700 kb). In addition, the patient 3 who harboring missense variants in the GATA binding domain of TRPS1 showed more severe craniofacial and skeletal phenotypes. Conclusions We describe four novel mutations and two novel phenotypes in five patients. The mutational and phenotypic spectrum of TRPS is broadened by our study on TRPS mutations. Our results reveal the significance of molecular analysis of TRPS1 for improving the clinical diagnosis of TRPS.https://doi.org/10.1002/mgg3.1417novel mutationnovel phenotypeTricho‐rhino‐phalangeal syndromeTRPS1 |
| spellingShingle | Chen Wang Yufei Xu Yanrong Qing Ruen Yao Niu Li Xiumin Wang Tingting Yu Jian Wang TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutations Molecular Genetics & Genomic Medicine novel mutation novel phenotype Tricho‐rhino‐phalangeal syndrome TRPS1 |
| title | TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutations |
| title_full | TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutations |
| title_fullStr | TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutations |
| title_full_unstemmed | TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutations |
| title_short | TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutations |
| title_sort | trps1 mutation detection in chinese patients with tricho rhino phalangeal syndrome and identification of four novel mutations |
| topic | novel mutation novel phenotype Tricho‐rhino‐phalangeal syndrome TRPS1 |
| url | https://doi.org/10.1002/mgg3.1417 |
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