From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1
A decade has passed since transmembrane coiled-coil domains 1 (TMCO1) defect syndrome was identified in 11 undiagnosed patients within the Old Order Amish of Northeastern Ohio—a disorder characterized by a distinctive craniofacial dysmorphism, skeletal anomalies and global developmental delay. Twent...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.652400/full |
| _version_ | 1829485818618576896 |
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| author | Helen Batchelor-Regan Helen Batchelor-Regan Baozhong Xin Aimin Zhou Heng Wang Heng Wang Heng Wang |
| author_facet | Helen Batchelor-Regan Helen Batchelor-Regan Baozhong Xin Aimin Zhou Heng Wang Heng Wang Heng Wang |
| author_sort | Helen Batchelor-Regan |
| collection | DOAJ |
| description | A decade has passed since transmembrane coiled-coil domains 1 (TMCO1) defect syndrome was identified in 11 undiagnosed patients within the Old Order Amish of Northeastern Ohio—a disorder characterized by a distinctive craniofacial dysmorphism, skeletal anomalies and global developmental delay. Twenty seven patients, from diverse ethnic groups, have been reported with pathogenic TMCO1 variants now recognized to cause cerebrofaciothoracic dysplasia (CFTD). The implication of previously uncharacterized TMCO1 within disease has instigated a 10-year journey to understand the function of TMCO1 protein in Ca2+ homeostasis. TMCO1 is an ER Ca2+ leak channel which facilitates Ca2+ leak upon ER “overload” through the novel Ca2+ load activated Ca2+ mechanism. This mini-review brings together the clinical and scientific advances made since the discovery of TMCO1 deficiency in disease, including broadened phenotype, understanding of pathophysiology, and implications to patient management of TMCO1 defect syndrome. |
| first_indexed | 2024-12-14T22:52:23Z |
| format | Article |
| id | doaj.art-f8867f4bd710482e856f1d3ae750628e |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-14T22:52:23Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-f8867f4bd710482e856f1d3ae750628e2022-12-21T22:44:40ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-05-011210.3389/fgene.2021.652400652400From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1Helen Batchelor-Regan0Helen Batchelor-Regan1Baozhong Xin2Aimin Zhou3Heng Wang4Heng Wang5Heng Wang6DDC Clinic Center for Special Needs Children, Middlefield, OH, United StatesClinical Genetics Department, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United KingdomDDC Clinic Center for Special Needs Children, Middlefield, OH, United StatesDepartment of Chemistry, Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH, United StatesDDC Clinic Center for Special Needs Children, Middlefield, OH, United StatesDepartment of Pediatrics, Rainbow Babies and Children’s Hospital, Cleveland, OH, United StatesDepartment of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, OH, United StatesA decade has passed since transmembrane coiled-coil domains 1 (TMCO1) defect syndrome was identified in 11 undiagnosed patients within the Old Order Amish of Northeastern Ohio—a disorder characterized by a distinctive craniofacial dysmorphism, skeletal anomalies and global developmental delay. Twenty seven patients, from diverse ethnic groups, have been reported with pathogenic TMCO1 variants now recognized to cause cerebrofaciothoracic dysplasia (CFTD). The implication of previously uncharacterized TMCO1 within disease has instigated a 10-year journey to understand the function of TMCO1 protein in Ca2+ homeostasis. TMCO1 is an ER Ca2+ leak channel which facilitates Ca2+ leak upon ER “overload” through the novel Ca2+ load activated Ca2+ mechanism. This mini-review brings together the clinical and scientific advances made since the discovery of TMCO1 deficiency in disease, including broadened phenotype, understanding of pathophysiology, and implications to patient management of TMCO1 defect syndrome.https://www.frontiersin.org/articles/10.3389/fgene.2021.652400/fullTMCO1CFTDTMCO1 defect syndromeCLAC channelcalciumcerebrofaciothoracic dysplasia |
| spellingShingle | Helen Batchelor-Regan Helen Batchelor-Regan Baozhong Xin Aimin Zhou Heng Wang Heng Wang Heng Wang From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1 Frontiers in Genetics TMCO1 CFTD TMCO1 defect syndrome CLAC channel calcium cerebrofaciothoracic dysplasia |
| title | From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1 |
| title_full | From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1 |
| title_fullStr | From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1 |
| title_full_unstemmed | From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1 |
| title_short | From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1 |
| title_sort | from disease description and gene discovery to functional cell pathway a decade long journey for tmco1 |
| topic | TMCO1 CFTD TMCO1 defect syndrome CLAC channel calcium cerebrofaciothoracic dysplasia |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.652400/full |
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