Compilation of Genotype and Phenotype Data in <i>GCDH</i>-LOVD for Variant Classification and Further Application
Glutaric aciduria type 1 (GA-1) is a rare but treatable autosomal-recessive neurometabolic disorder of lysin metabolism caused by biallelic pathogenic variants in glutaryl-CoA dehydrogenase gene (<i>GCDH</i>) that lead to deficiency of GCDH protein. Without treatment, this enzyme defect...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/12/2218 |
| _version_ | 1797380883842334720 |
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| author | Alexandra Tibelius Christina Evers Sabrina Oeser Isabelle Rinke Anna Jauch Katrin Hinderhofer |
| author_facet | Alexandra Tibelius Christina Evers Sabrina Oeser Isabelle Rinke Anna Jauch Katrin Hinderhofer |
| author_sort | Alexandra Tibelius |
| collection | DOAJ |
| description | Glutaric aciduria type 1 (GA-1) is a rare but treatable autosomal-recessive neurometabolic disorder of lysin metabolism caused by biallelic pathogenic variants in glutaryl-CoA dehydrogenase gene (<i>GCDH</i>) that lead to deficiency of GCDH protein. Without treatment, this enzyme defect causes a neurological phenotype characterized by movement disorder and cognitive impairment. Based on a comprehensive literature search, we established a large dataset of <i>GCDH</i> variants using the Leiden Open Variation Database (LOVD) to summarize the known genotypes and the clinical and biochemical phenotypes associated with GA-1. With these data, we developed a <i>GCDH</i>-specific variation classification framework based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. We used this framework to reclassify published variants and to describe their geographic distribution, both of which have practical implications for the molecular genetic diagnosis of GA-1. The freely available <i>GCDH</i>-specific LOVD dataset provides a basis for diagnostic laboratories and researchers to further optimize their knowledge and molecular diagnosis of this rare disease. |
| first_indexed | 2024-03-08T20:43:27Z |
| format | Article |
| id | doaj.art-0f98d8da7622496084cc99137b863b42 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-08T20:43:27Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-0f98d8da7622496084cc99137b863b422023-12-22T14:11:22ZengMDPI AGGenes2073-44252023-12-011412221810.3390/genes14122218Compilation of Genotype and Phenotype Data in <i>GCDH</i>-LOVD for Variant Classification and Further ApplicationAlexandra Tibelius0Christina Evers1Sabrina Oeser2Isabelle Rinke3Anna Jauch4Katrin Hinderhofer5Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, 69120 Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, 69120 Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, 69120 Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, 69120 Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, 69120 Heidelberg, GermanyGlutaric aciduria type 1 (GA-1) is a rare but treatable autosomal-recessive neurometabolic disorder of lysin metabolism caused by biallelic pathogenic variants in glutaryl-CoA dehydrogenase gene (<i>GCDH</i>) that lead to deficiency of GCDH protein. Without treatment, this enzyme defect causes a neurological phenotype characterized by movement disorder and cognitive impairment. Based on a comprehensive literature search, we established a large dataset of <i>GCDH</i> variants using the Leiden Open Variation Database (LOVD) to summarize the known genotypes and the clinical and biochemical phenotypes associated with GA-1. With these data, we developed a <i>GCDH</i>-specific variation classification framework based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. We used this framework to reclassify published variants and to describe their geographic distribution, both of which have practical implications for the molecular genetic diagnosis of GA-1. The freely available <i>GCDH</i>-specific LOVD dataset provides a basis for diagnostic laboratories and researchers to further optimize their knowledge and molecular diagnosis of this rare disease.https://www.mdpi.com/2073-4425/14/12/2218glutaric aciduriaglutaric acidemiaglutaryl-CoA dehydrogenase<i>GCDH</i>inborn errors of metabolismvariant interpretation |
| spellingShingle | Alexandra Tibelius Christina Evers Sabrina Oeser Isabelle Rinke Anna Jauch Katrin Hinderhofer Compilation of Genotype and Phenotype Data in <i>GCDH</i>-LOVD for Variant Classification and Further Application Genes glutaric aciduria glutaric acidemia glutaryl-CoA dehydrogenase <i>GCDH</i> inborn errors of metabolism variant interpretation |
| title | Compilation of Genotype and Phenotype Data in <i>GCDH</i>-LOVD for Variant Classification and Further Application |
| title_full | Compilation of Genotype and Phenotype Data in <i>GCDH</i>-LOVD for Variant Classification and Further Application |
| title_fullStr | Compilation of Genotype and Phenotype Data in <i>GCDH</i>-LOVD for Variant Classification and Further Application |
| title_full_unstemmed | Compilation of Genotype and Phenotype Data in <i>GCDH</i>-LOVD for Variant Classification and Further Application |
| title_short | Compilation of Genotype and Phenotype Data in <i>GCDH</i>-LOVD for Variant Classification and Further Application |
| title_sort | compilation of genotype and phenotype data in i gcdh i lovd for variant classification and further application |
| topic | glutaric aciduria glutaric acidemia glutaryl-CoA dehydrogenase <i>GCDH</i> inborn errors of metabolism variant interpretation |
| url | https://www.mdpi.com/2073-4425/14/12/2218 |
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