The diagnosis of inherited metabolic diseases by microarray gene expression profiling
<p>Abstract</p> <p>Background</p> <p>Inherited metabolic diseases (IMDs) comprise a diverse group of generally progressive genetic metabolic disorders of variable clinical presentations and severity. We have undertaken a study using microarray gene expression profiling...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-12-01
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| Series: | Orphanet Journal of Rare Diseases |
| Online Access: | http://www.ojrd.com/content/5/1/34 |
| _version_ | 1818641046277455872 |
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| author | Taanman Jan-Willem Champion Michael P Perrett David Young Bryan D Chaplin Tracy Schulz Reiner Arenas Hernandez Monica Fensom Anthony Marinaki Anthony M |
| author_facet | Taanman Jan-Willem Champion Michael P Perrett David Young Bryan D Chaplin Tracy Schulz Reiner Arenas Hernandez Monica Fensom Anthony Marinaki Anthony M |
| author_sort | Taanman Jan-Willem |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inherited metabolic diseases (IMDs) comprise a diverse group of generally progressive genetic metabolic disorders of variable clinical presentations and severity. We have undertaken a study using microarray gene expression profiling of cultured fibroblasts to investigate 68 patients with a broad range of suspected metabolic disorders, including defects of lysosomal, mitochondrial, peroxisomal, fatty acid, carbohydrate, amino acid, molybdenum cofactor, and purine and pyrimidine metabolism. We aimed to define gene expression signatures characteristic of defective metabolic pathways.</p> <p>Methods</p> <p>Total mRNA extracted from cultured fibroblast cell lines was hybridized to Affymetrix U133 Plus 2.0 arrays. Expression data was analyzed for the presence of a gene expression signature characteristic of an inherited metabolic disorder and for genes expressing significantly decreased levels of mRNA.</p> <p>Results</p> <p>No characteristic signatures were found. However, in 16% of cases, disease-associated nonsense and frameshift mutations generating premature termination codons resulted in significantly decreased mRNA expression of the defective gene. The microarray assay detected these changes with high sensitivity and specificity.</p> <p>Conclusion</p> <p>In patients with a suspected familial metabolic disorder where initial screening tests have proven uninformative, microarray gene expression profiling may contribute significantly to the identification of the genetic defect, shortcutting the diagnostic cascade.</p> |
| first_indexed | 2024-12-16T23:20:56Z |
| format | Article |
| id | doaj.art-83dfb016925d47a0a0921359cabbcc18 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-16T23:20:56Z |
| publishDate | 2010-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-83dfb016925d47a0a0921359cabbcc182022-12-21T22:12:09ZengBMCOrphanet Journal of Rare Diseases1750-11722010-12-01513410.1186/1750-1172-5-34The diagnosis of inherited metabolic diseases by microarray gene expression profilingTaanman Jan-WillemChampion Michael PPerrett DavidYoung Bryan DChaplin TracySchulz ReinerArenas Hernandez MonicaFensom AnthonyMarinaki Anthony M<p>Abstract</p> <p>Background</p> <p>Inherited metabolic diseases (IMDs) comprise a diverse group of generally progressive genetic metabolic disorders of variable clinical presentations and severity. We have undertaken a study using microarray gene expression profiling of cultured fibroblasts to investigate 68 patients with a broad range of suspected metabolic disorders, including defects of lysosomal, mitochondrial, peroxisomal, fatty acid, carbohydrate, amino acid, molybdenum cofactor, and purine and pyrimidine metabolism. We aimed to define gene expression signatures characteristic of defective metabolic pathways.</p> <p>Methods</p> <p>Total mRNA extracted from cultured fibroblast cell lines was hybridized to Affymetrix U133 Plus 2.0 arrays. Expression data was analyzed for the presence of a gene expression signature characteristic of an inherited metabolic disorder and for genes expressing significantly decreased levels of mRNA.</p> <p>Results</p> <p>No characteristic signatures were found. However, in 16% of cases, disease-associated nonsense and frameshift mutations generating premature termination codons resulted in significantly decreased mRNA expression of the defective gene. The microarray assay detected these changes with high sensitivity and specificity.</p> <p>Conclusion</p> <p>In patients with a suspected familial metabolic disorder where initial screening tests have proven uninformative, microarray gene expression profiling may contribute significantly to the identification of the genetic defect, shortcutting the diagnostic cascade.</p>http://www.ojrd.com/content/5/1/34 |
| spellingShingle | Taanman Jan-Willem Champion Michael P Perrett David Young Bryan D Chaplin Tracy Schulz Reiner Arenas Hernandez Monica Fensom Anthony Marinaki Anthony M The diagnosis of inherited metabolic diseases by microarray gene expression profiling Orphanet Journal of Rare Diseases |
| title | The diagnosis of inherited metabolic diseases by microarray gene expression profiling |
| title_full | The diagnosis of inherited metabolic diseases by microarray gene expression profiling |
| title_fullStr | The diagnosis of inherited metabolic diseases by microarray gene expression profiling |
| title_full_unstemmed | The diagnosis of inherited metabolic diseases by microarray gene expression profiling |
| title_short | The diagnosis of inherited metabolic diseases by microarray gene expression profiling |
| title_sort | diagnosis of inherited metabolic diseases by microarray gene expression profiling |
| url | http://www.ojrd.com/content/5/1/34 |
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