Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy Treatment
Hutchinson-Gilford progeria syndrome (HGPS) is one of the most severe disorders among laminopathies—a heterogeneous group of genetic diseases with a molecular background based on mutations in the <i>LMNA</i> gene and genes coding for interacting proteins. HGPS is characterized...
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MDPI AG
2019-01-01
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| author | Katarzyna Piekarowicz Magdalena Machowska Volha Dzianisava Ryszard Rzepecki |
| author_facet | Katarzyna Piekarowicz Magdalena Machowska Volha Dzianisava Ryszard Rzepecki |
| author_sort | Katarzyna Piekarowicz |
| collection | DOAJ |
| description | Hutchinson-Gilford progeria syndrome (HGPS) is one of the most severe disorders among laminopathies—a heterogeneous group of genetic diseases with a molecular background based on mutations in the <i>LMNA</i> gene and genes coding for interacting proteins. HGPS is characterized by the presence of aging-associated symptoms, including lack of subcutaneous fat, alopecia, swollen veins, growth retardation, age spots, joint contractures, osteoporosis, cardiovascular pathology, and death due to heart attacks and strokes in childhood. <i>LMNA</i> codes for two major, alternatively spliced transcripts, give rise to lamin A and lamin C proteins. Mutations in the <i>LMNA</i> gene alone, depending on the nature and location, may result in the expression of abnormal protein or loss of protein expression and cause at least 11 disease phenotypes, differing in severity and affected tissue. <i>LMNA</i> gene-related HGPS is caused by a single mutation in the <i>LMNA</i> gene in exon 11. The mutation c.1824C > T results in activation of the cryptic donor splice site, which leads to the synthesis of progerin protein lacking 50 amino acids. The accumulation of progerin is the reason for appearance of the phenotype. In this review, we discuss current knowledge on the molecular mechanisms underlying the development of HGPS and provide a critical analysis of current research trends in this field. We also discuss the mouse models available so far, the current status of treatment of the disease, and future prospects for the development of efficient therapies, including gene therapy for HGPS. |
| first_indexed | 2024-03-12T19:36:00Z |
| format | Article |
| id | doaj.art-f51de942783f435a8ca465f012471f46 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:36:00Z |
| publishDate | 2019-01-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-f51de942783f435a8ca465f012471f462023-08-02T04:13:35ZengMDPI AGCells2073-44092019-01-01828810.3390/cells8020088cells8020088Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy TreatmentKatarzyna Piekarowicz0Magdalena Machowska1Volha Dzianisava2Ryszard Rzepecki3Laboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Fryderyka Joliot-Curie 14a, 50-383 Wroclaw, PolandLaboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Fryderyka Joliot-Curie 14a, 50-383 Wroclaw, PolandLaboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Fryderyka Joliot-Curie 14a, 50-383 Wroclaw, PolandLaboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Fryderyka Joliot-Curie 14a, 50-383 Wroclaw, PolandHutchinson-Gilford progeria syndrome (HGPS) is one of the most severe disorders among laminopathies—a heterogeneous group of genetic diseases with a molecular background based on mutations in the <i>LMNA</i> gene and genes coding for interacting proteins. HGPS is characterized by the presence of aging-associated symptoms, including lack of subcutaneous fat, alopecia, swollen veins, growth retardation, age spots, joint contractures, osteoporosis, cardiovascular pathology, and death due to heart attacks and strokes in childhood. <i>LMNA</i> codes for two major, alternatively spliced transcripts, give rise to lamin A and lamin C proteins. Mutations in the <i>LMNA</i> gene alone, depending on the nature and location, may result in the expression of abnormal protein or loss of protein expression and cause at least 11 disease phenotypes, differing in severity and affected tissue. <i>LMNA</i> gene-related HGPS is caused by a single mutation in the <i>LMNA</i> gene in exon 11. The mutation c.1824C > T results in activation of the cryptic donor splice site, which leads to the synthesis of progerin protein lacking 50 amino acids. The accumulation of progerin is the reason for appearance of the phenotype. In this review, we discuss current knowledge on the molecular mechanisms underlying the development of HGPS and provide a critical analysis of current research trends in this field. We also discuss the mouse models available so far, the current status of treatment of the disease, and future prospects for the development of efficient therapies, including gene therapy for HGPS.https://www.mdpi.com/2073-4409/8/2/88HGPSlaminopathylamin A/Cprogeringene therapymiR9 |
| spellingShingle | Katarzyna Piekarowicz Magdalena Machowska Volha Dzianisava Ryszard Rzepecki Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy Treatment Cells HGPS laminopathy lamin A/C progerin gene therapy miR9 |
| title | Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy Treatment |
| title_full | Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy Treatment |
| title_fullStr | Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy Treatment |
| title_full_unstemmed | Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy Treatment |
| title_short | Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy Treatment |
| title_sort | hutchinson gilford progeria syndrome current status and prospects for gene therapy treatment |
| topic | HGPS laminopathy lamin A/C progerin gene therapy miR9 |
| url | https://www.mdpi.com/2073-4409/8/2/88 |
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