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Genotype-based databases for variants causing rare diseases.
Gene. 2014 Oct 15; 550(1):136-40.GENE

Abstract

Inherited diseases are the result of DNA sequence changes. In recessive diseases, the clinical phenotype results from the combined functional effects of variants in both copies of the gene. In some diseases there is often considerable variability of clinical presentation or disease severity, which may be predicted by the genotype. Additional effects may be triggered by environmental factors, as well as genetic modifiers which could be nucleotide polymorphisms in related genes, e.g. maternal ApoE or ABCA1 genotypes which may have an influence on the phenotype of SLOS individuals. Here we report the establishment of genotype variation databases for various rare diseases which provide individual clinical phenotypes associated with genotypes and include data about possible genetic modifiers. These databases aim to be an easy public access to information on rare and private variants with clinical data, which will facilitate the interpretation of genetic variants. The created databases include ACAD8 (isobutyryl-CoA dehydrogenase deficiency (IBD)), ACADSB (short-chain acyl-CoA dehydrogenase (SCAD) deficiency), AUH (3-methylglutaconic aciduria (3-MGCA)), DHCR7 (Smith-Lemli-Opitz syndrome), HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency), HSD17B10 (17-beta-hydroxysteroid dehydrogenase X deficiency), FKBP14 (Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss; EDSKMH) and ROGDI (Kohlschütter-Tönz syndrome). These genes have been selected because of our specific research interests in these rare and metabolic diseases. The aim of the database was to include all identified individuals with variants in these specific genes. Identical genotypes are listed multiple times if they were found in several patients, phenotypic descriptions and biochemical data are included as detailed as possible in view also of validating the proposed pathogenicity of these genotypes. For DHCR7 genetic modifier data (maternal APOE and ABCA1 genotypes) is also included. Databases are available at http://databases.lovd.nl/shared/genes and will be updated based on periodic literature reviews and submitted reports.

Authors+Show Affiliations

Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.Department of Paediatrics and Adolescent Medicine, Hospital Salzburg, Salzburg, Austria.Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria. Electronic address: witsch-baumgartner@i-med.ac.at.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25111118

Citation

Lanthaler, Barbara, et al. "Genotype-based Databases for Variants Causing Rare Diseases." Gene, vol. 550, no. 1, 2014, pp. 136-40.
Lanthaler B, Wieser S, Deutschmann A, et al. Genotype-based databases for variants causing rare diseases. Gene. 2014;550(1):136-40.
Lanthaler, B., Wieser, S., Deutschmann, A., Schossig, A., Fauth, C., Zschocke, J., & Witsch-Baumgartner, M. (2014). Genotype-based databases for variants causing rare diseases. Gene, 550(1), 136-40. https://doi.org/10.1016/j.gene.2014.08.016
Lanthaler B, et al. Genotype-based Databases for Variants Causing Rare Diseases. Gene. 2014 Oct 15;550(1):136-40. PubMed PMID: 25111118.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-based databases for variants causing rare diseases. AU - Lanthaler,Barbara, AU - Wieser,Stefanie, AU - Deutschmann,Andrea, AU - Schossig,Anna, AU - Fauth,Christine, AU - Zschocke,Johannes, AU - Witsch-Baumgartner,Martina, Y1 - 2014/08/08/ PY - 2014/01/21/received PY - 2014/04/23/revised PY - 2014/08/07/accepted PY - 2014/8/12/entrez PY - 2014/8/12/pubmed PY - 2014/12/15/medline KW - ACAD8 KW - ACADSB KW - AUH KW - DHCR7 KW - FKBP14 KW - HMGCS2 KW - HSD17B10 KW - LOVD 3.0 KW - ROGDI SP - 136 EP - 40 JF - Gene JO - Gene VL - 550 IS - 1 N2 - Inherited diseases are the result of DNA sequence changes. In recessive diseases, the clinical phenotype results from the combined functional effects of variants in both copies of the gene. In some diseases there is often considerable variability of clinical presentation or disease severity, which may be predicted by the genotype. Additional effects may be triggered by environmental factors, as well as genetic modifiers which could be nucleotide polymorphisms in related genes, e.g. maternal ApoE or ABCA1 genotypes which may have an influence on the phenotype of SLOS individuals. Here we report the establishment of genotype variation databases for various rare diseases which provide individual clinical phenotypes associated with genotypes and include data about possible genetic modifiers. These databases aim to be an easy public access to information on rare and private variants with clinical data, which will facilitate the interpretation of genetic variants. The created databases include ACAD8 (isobutyryl-CoA dehydrogenase deficiency (IBD)), ACADSB (short-chain acyl-CoA dehydrogenase (SCAD) deficiency), AUH (3-methylglutaconic aciduria (3-MGCA)), DHCR7 (Smith-Lemli-Opitz syndrome), HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency), HSD17B10 (17-beta-hydroxysteroid dehydrogenase X deficiency), FKBP14 (Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss; EDSKMH) and ROGDI (Kohlschütter-Tönz syndrome). These genes have been selected because of our specific research interests in these rare and metabolic diseases. The aim of the database was to include all identified individuals with variants in these specific genes. Identical genotypes are listed multiple times if they were found in several patients, phenotypic descriptions and biochemical data are included as detailed as possible in view also of validating the proposed pathogenicity of these genotypes. For DHCR7 genetic modifier data (maternal APOE and ABCA1 genotypes) is also included. Databases are available at http://databases.lovd.nl/shared/genes and will be updated based on periodic literature reviews and submitted reports. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/25111118/Genotype_based_databases_for_variants_causing_rare_diseases_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(14)00929-9 DB - PRIME DP - Unbound Medicine ER -