Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis
Osteopetrosis is characterized by increased bone density caused by decreased osteoclasts or dysfunction of their differentiation and absorption properties, usually caused by biallelic variants of the TCIRG1(OMIM:604592)and CLCN7(OMIM:602727) genes. Herein, the clinical, biochemical, and radiological...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Pediatrics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1096770/full |
| _version_ | 1797871426215084032 |
|---|---|
| author | Yu Chen Yu Chen Lina Zhou Xianmin Guan Xianhao Wen Jie Yu Ying Dou Ying Dou |
| author_facet | Yu Chen Yu Chen Lina Zhou Xianmin Guan Xianhao Wen Jie Yu Ying Dou Ying Dou |
| author_sort | Yu Chen |
| collection | DOAJ |
| description | Osteopetrosis is characterized by increased bone density caused by decreased osteoclasts or dysfunction of their differentiation and absorption properties, usually caused by biallelic variants of the TCIRG1(OMIM:604592)and CLCN7(OMIM:602727) genes. Herein, the clinical, biochemical, and radiological manifestations of osteopetrosis in four Chinese children are described. Whole-exome sequencing identified compound heterozygous variants of the CLCN7 and TCIRG1 genes in these patients. In Patient 1, two novel variants were identified in CLCN7:c.880T > G(p.F294V) and c.686C > G(p.S229X). Patient 2 harbored previously reported a single gene variant c.643G > A(p.G215R) in CLCN7. Patient 3 had a novel variant c.569A > G(p.N190S) and a novel frameshift variant c.1113dupG(p.N372fs) in CLCN7. Patient 4 had a frameshift variant c.43delA(p.K15fs) and variant c.C1360T in TCIRG1, resulting in the formation of a premature termination codon (p.R454X), both of which were reported previously. Our results expand the spectrum of identified genetic variation in osteopetrosis and provide a deeper understanding of the relations between genotype and clinical characteristics of this disorder. |
| first_indexed | 2024-04-10T00:43:48Z |
| format | Article |
| id | doaj.art-42ba3568a19d4b30ba16d1cab21f2900 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-04-10T00:43:48Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-42ba3568a19d4b30ba16d1cab21f29002023-03-14T04:39:51ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-03-011110.3389/fped.2023.10967701096770Case report: Gene mutations and clinical characteristics of four patients with osteopetrosisYu Chen0Yu Chen1Lina Zhou2Xianmin Guan3Xianhao Wen4Jie Yu5Ying Dou6Ying Dou7National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hematological Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hematological Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hematological Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hematological Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hematological Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaOsteopetrosis is characterized by increased bone density caused by decreased osteoclasts or dysfunction of their differentiation and absorption properties, usually caused by biallelic variants of the TCIRG1(OMIM:604592)and CLCN7(OMIM:602727) genes. Herein, the clinical, biochemical, and radiological manifestations of osteopetrosis in four Chinese children are described. Whole-exome sequencing identified compound heterozygous variants of the CLCN7 and TCIRG1 genes in these patients. In Patient 1, two novel variants were identified in CLCN7:c.880T > G(p.F294V) and c.686C > G(p.S229X). Patient 2 harbored previously reported a single gene variant c.643G > A(p.G215R) in CLCN7. Patient 3 had a novel variant c.569A > G(p.N190S) and a novel frameshift variant c.1113dupG(p.N372fs) in CLCN7. Patient 4 had a frameshift variant c.43delA(p.K15fs) and variant c.C1360T in TCIRG1, resulting in the formation of a premature termination codon (p.R454X), both of which were reported previously. Our results expand the spectrum of identified genetic variation in osteopetrosis and provide a deeper understanding of the relations between genotype and clinical characteristics of this disorder.https://www.frontiersin.org/articles/10.3389/fped.2023.1096770/fullosteopetrosisCLCN7TCIRG1mutationvariants |
| spellingShingle | Yu Chen Yu Chen Lina Zhou Xianmin Guan Xianhao Wen Jie Yu Ying Dou Ying Dou Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis Frontiers in Pediatrics osteopetrosis CLCN7 TCIRG1 mutation variants |
| title | Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis |
| title_full | Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis |
| title_fullStr | Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis |
| title_full_unstemmed | Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis |
| title_short | Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis |
| title_sort | case report gene mutations and clinical characteristics of four patients with osteopetrosis |
| topic | osteopetrosis CLCN7 TCIRG1 mutation variants |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1096770/full |
| work_keys_str_mv | AT yuchen casereportgenemutationsandclinicalcharacteristicsoffourpatientswithosteopetrosis AT yuchen casereportgenemutationsandclinicalcharacteristicsoffourpatientswithosteopetrosis AT linazhou casereportgenemutationsandclinicalcharacteristicsoffourpatientswithosteopetrosis AT xianminguan casereportgenemutationsandclinicalcharacteristicsoffourpatientswithosteopetrosis AT xianhaowen casereportgenemutationsandclinicalcharacteristicsoffourpatientswithosteopetrosis AT jieyu casereportgenemutationsandclinicalcharacteristicsoffourpatientswithosteopetrosis AT yingdou casereportgenemutationsandclinicalcharacteristicsoffourpatientswithosteopetrosis AT yingdou casereportgenemutationsandclinicalcharacteristicsoffourpatientswithosteopetrosis |