title: Genotype-based databases for variants causing rare diseases.
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.affiliation: Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lanthaler
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Hospital Salzburg, Salzburg, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wieser
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Deutschmann
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Schossig
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Fauth
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria. Electronic address: witsch-baumgartner@i-med.ac.at.
authors.forename: Martina
authors.initials: M
authors.lastname: Witsch-Baumgartner
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency / Q000235:genetics; D044944:Acyl-CoA Dehydrogenases / Q000235:genetics; D000567:Amelogenesis Imperfecta / Q000235:genetics / Q000473:pathology; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D030541:Databases, Genetic; D003704:Dementia / Q000235:genetics / Q000473:pathology; D004535:Ehlers-Danlos Syndrome / Q000235:genetics / Q000473:pathology; D004746:Enoyl-CoA Hydratase / Q000235:genetics; D004827:Epilepsy / Q000235:genetics / Q000473:pathology; D056726:Genetic Association Studies / Q000379:methods / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000172:deficiency / Q000235:genetics; D007003:Hypoglycemia / Q000235:genetics / Q000473:pathology; D020407:Internet; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D019696:Peptidylprolyl Isomerase / Q000235:genetics; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics; D035583:Rare Diseases / Q000235:genetics* / Q000473:pathology; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics / Q000473:pathology
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D008565:Membrane Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C572461:ROGDI protein, human; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; D044944:Acyl-CoA Dehydrogenases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase; C122081:ACAD8 protein, human; D042964:Acyl-CoA Dehydrogenase; D006904:Hydroxymethylglutaryl-CoA Synthase; C092554:AUH protein, human; D004746:Enoyl-CoA Hydratase; C572897:FKBP14 protein, human; D019696:Peptidylprolyl Isomerase
keywords: ACAD8; ACADSB; AUH; DHCR7; FKBP14; HMGCS2; HSD17B10; LOVD 3.0; ROGDI