Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18
Background. Bone mineral density quantitative trait locus 18 (BMND18, OMIM #300910) is a type of early-onset osteogenesis imperfecta (OI) caused by loss-of-function mutations in the PLS3 gene, which encodes plastin-3, a key protein in the formation of actin bundles throughout the cytoskeleton. Here,...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2018/8953217 |
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| author | Ting Chen Haiying Wu Chenxi Zhang Jiarong Feng Linqi Chen Rongrong Xie Fengyun Wang Xiuli Chen Huiting Zhou Hui Sun Fei Xiao |
| author_facet | Ting Chen Haiying Wu Chenxi Zhang Jiarong Feng Linqi Chen Rongrong Xie Fengyun Wang Xiuli Chen Huiting Zhou Hui Sun Fei Xiao |
| author_sort | Ting Chen |
| collection | DOAJ |
| description | Background. Bone mineral density quantitative trait locus 18 (BMND18, OMIM #300910) is a type of early-onset osteogenesis imperfecta (OI) caused by loss-of-function mutations in the PLS3 gene, which encodes plastin-3, a key protein in the formation of actin bundles throughout the cytoskeleton. Here, we report a patient with PLS3 mutation caused BMND18 and evaluated all the reported disease-causing mutations by bioinformatic analysis. Methods. Targeted gene sequencing was performed to find the disease-causing mutation in our patient. Bioinformatic analyses mainly including homology modelling and molecular dynamics stimulation were conducted to explore the impact of the previously reported mutations on plastin-3. Results. Gene sequencing showed a novel nonsense mutation (c.745G > T, p.E249X), which locates at a highly conserved region containing residues p.240–266 (LOOP-1) in the PLS3 gene. Further bioinformatic analyses of the previously reported mutations revealed that LOOP-1 is predicted to physically connect the calponin-homology 1 (CH1) and CH2 domains of the ABD1 fragment and spatially locates within the interface of ABD1 and ABD2. It is crucial to the conformation transition and actin-binding function of plastin-3. Conclusions. This report identified a novel mutation that truncates the PLS3 gene. Moreover, bioinformatic analyses of the previous reported mutations in PLS3 gene lead us to find a critical LOOP-1 region of plastin-3 mutations at which may be detrimental to the integral conformation of plastin-3 and thus affect its binding to actin filament. |
| format | Article |
| id | doaj-art-7228929ca1cd48b5a03bb1aaefcfcdd4 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-7228929ca1cd48b5a03bb1aaefcfcdd42025-08-20T03:33:43ZengWileyInternational Journal of Endocrinology1687-83371687-83452018-01-01201810.1155/2018/89532178953217Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18Ting Chen0Haiying Wu1Chenxi Zhang2Jiarong Feng3Linqi Chen4Rongrong Xie5Fengyun Wang6Xiuli Chen7Huiting Zhou8Hui Sun9Fei Xiao10Department of Endocrinology, Metabolism, and Genetic Diseases, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Endocrinology, Metabolism, and Genetic Diseases, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Soochow University, Suzhou, Jiangsu, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Soochow University, Suzhou, Jiangsu, ChinaDepartment of Endocrinology, Metabolism, and Genetic Diseases, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Endocrinology, Metabolism, and Genetic Diseases, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Endocrinology, Metabolism, and Genetic Diseases, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Endocrinology, Metabolism, and Genetic Diseases, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaInstitute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Endocrinology, Metabolism, and Genetic Diseases, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Soochow University, Suzhou, Jiangsu, ChinaBackground. Bone mineral density quantitative trait locus 18 (BMND18, OMIM #300910) is a type of early-onset osteogenesis imperfecta (OI) caused by loss-of-function mutations in the PLS3 gene, which encodes plastin-3, a key protein in the formation of actin bundles throughout the cytoskeleton. Here, we report a patient with PLS3 mutation caused BMND18 and evaluated all the reported disease-causing mutations by bioinformatic analysis. Methods. Targeted gene sequencing was performed to find the disease-causing mutation in our patient. Bioinformatic analyses mainly including homology modelling and molecular dynamics stimulation were conducted to explore the impact of the previously reported mutations on plastin-3. Results. Gene sequencing showed a novel nonsense mutation (c.745G > T, p.E249X), which locates at a highly conserved region containing residues p.240–266 (LOOP-1) in the PLS3 gene. Further bioinformatic analyses of the previously reported mutations revealed that LOOP-1 is predicted to physically connect the calponin-homology 1 (CH1) and CH2 domains of the ABD1 fragment and spatially locates within the interface of ABD1 and ABD2. It is crucial to the conformation transition and actin-binding function of plastin-3. Conclusions. This report identified a novel mutation that truncates the PLS3 gene. Moreover, bioinformatic analyses of the previous reported mutations in PLS3 gene lead us to find a critical LOOP-1 region of plastin-3 mutations at which may be detrimental to the integral conformation of plastin-3 and thus affect its binding to actin filament.http://dx.doi.org/10.1155/2018/8953217 |
| spellingShingle | Ting Chen Haiying Wu Chenxi Zhang Jiarong Feng Linqi Chen Rongrong Xie Fengyun Wang Xiuli Chen Huiting Zhou Hui Sun Fei Xiao Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18 International Journal of Endocrinology |
| title | Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18 |
| title_full | Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18 |
| title_fullStr | Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18 |
| title_full_unstemmed | Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18 |
| title_short | Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18 |
| title_sort | clinical genetics and bioinformatic characterization of mutations affecting an essential region of pls3 in patients with bmnd18 |
| url | http://dx.doi.org/10.1155/2018/8953217 |
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