Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-Summary
Mutations in genes encoding proteins associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex within the nuclear envelope cause different diseases with varying phenotypes including skeletal muscle, cardiac, metabolic, or nervous system pathologies. There is some understanding of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/24/4065 |
| _version_ | 1797460985049513984 |
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| author | Emily C. Storey Heidi R. Fuller |
| author_facet | Emily C. Storey Heidi R. Fuller |
| author_sort | Emily C. Storey |
| collection | DOAJ |
| description | Mutations in genes encoding proteins associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex within the nuclear envelope cause different diseases with varying phenotypes including skeletal muscle, cardiac, metabolic, or nervous system pathologies. There is some understanding of the structure of LINC complex-associated proteins and how they interact, but it is unclear how mutations in genes encoding them can cause the same disease, and different diseases with different phenotypes. Here, published mutations in LINC complex-associated proteins were systematically reviewed and analyzed to ascertain whether patterns exist between the genetic sequence variants and clinical phenotypes. This revealed <i>LMNA</i> is the only LINC complex-associated gene in which mutations commonly cause distinct conditions, and there are no clear genotype-phenotype correlations. Clusters of <i>LMNA</i> variants causing striated muscle disease are located in exons 1 and 6, and metabolic disease-associated <i>LMNA</i> variants are frequently found in the tail of lamin A/C. Additionally, exon 6 of the emerin gene, <i>EMD</i>, may be a mutation “hot-spot”, and diseases related to <i>SYNE1</i>, encoding nesprin-1, are most often caused by nonsense type mutations. These results provide insight into the diverse roles of LINC-complex proteins in human disease and provide direction for future gene-targeted therapy development. |
| first_indexed | 2024-03-09T17:12:55Z |
| format | Article |
| id | doaj.art-fd5ff9bd51ca43c8987b8db11f751ebe |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:12:55Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fd5ff9bd51ca43c8987b8db11f751ebe2023-11-24T13:55:13ZengMDPI AGCells2073-44092022-12-011124406510.3390/cells11244065Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-SummaryEmily C. Storey0Heidi R. Fuller1School of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, UKSchool of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, UKMutations in genes encoding proteins associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex within the nuclear envelope cause different diseases with varying phenotypes including skeletal muscle, cardiac, metabolic, or nervous system pathologies. There is some understanding of the structure of LINC complex-associated proteins and how they interact, but it is unclear how mutations in genes encoding them can cause the same disease, and different diseases with different phenotypes. Here, published mutations in LINC complex-associated proteins were systematically reviewed and analyzed to ascertain whether patterns exist between the genetic sequence variants and clinical phenotypes. This revealed <i>LMNA</i> is the only LINC complex-associated gene in which mutations commonly cause distinct conditions, and there are no clear genotype-phenotype correlations. Clusters of <i>LMNA</i> variants causing striated muscle disease are located in exons 1 and 6, and metabolic disease-associated <i>LMNA</i> variants are frequently found in the tail of lamin A/C. Additionally, exon 6 of the emerin gene, <i>EMD</i>, may be a mutation “hot-spot”, and diseases related to <i>SYNE1</i>, encoding nesprin-1, are most often caused by nonsense type mutations. These results provide insight into the diverse roles of LINC-complex proteins in human disease and provide direction for future gene-targeted therapy development.https://www.mdpi.com/2073-4409/11/24/4065LINC complexnuclear envelopelaminopathieslamin A/C<i>LMNA</i><i>SYNE1</i> |
| spellingShingle | Emily C. Storey Heidi R. Fuller Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-Summary Cells LINC complex nuclear envelope laminopathies lamin A/C <i>LMNA</i> <i>SYNE1</i> |
| title | Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-Summary |
| title_full | Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-Summary |
| title_fullStr | Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-Summary |
| title_full_unstemmed | Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-Summary |
| title_short | Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-Summary |
| title_sort | genotype phenotype correlations in human diseases caused by mutations of linc complex associated genes a systematic review and meta summary |
| topic | LINC complex nuclear envelope laminopathies lamin A/C <i>LMNA</i> <i>SYNE1</i> |
| url | https://www.mdpi.com/2073-4409/11/24/4065 |
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