title: Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice.
abstract: Next generation sequencing (NGS) is a rapidly developing area in genetics. Utilizing this technology in the management of disorders with complex genetic background and not recurrent mutation hot spots can be extremely useful. In this study, we applied NGS, namely semiconductor sequencing to determine the most significant osteogenesis imperfecta-related genetic variants in the clinical practice. We selected genes coding collagen type I alpha-1 and-2 (COL1A1, COL1A2) which are responsible for more than 90% of all cases. CRTAP and LEPRE1/P3H1 genes involved in the background of the recessive forms with relatively high frequency (type VII and VIII) represent less than 10% of the disease. In our six patients (1-41 years), we identified 23 different variants. We found a total of 14 single nucleotide variants (SNV) in COL1A1 and COL1A2, 5 in CRTAP and 4 in LEPRE1. Two novel and two already well-established pathogenic SNVs have been identified. Among the newly recognized mutations, one results in an amino acid change and one of them is a stop codon. We have shown that a new full-scale cost-effective NGS method can be developed and utilized to supplement diagnostic process of osteogenesis imperfecta with molecular genetic data in clinical practice.
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Korányi S. u. 2/a, Hungary.|PentaCore Laboratory, H-1094 Budapest, Bokréta u. 5, Hungary.
authors.forename: Kristóf
authors.initials: K
authors.lastname: Árvai
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Korányi S. u. 2/a, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Horváth
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Korányi S. u. 2/a, Hungary.|PentaCore Laboratory, H-1094 Budapest, Bokréta u. 5, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Balla
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Korányi S. u. 2/a, Hungary.|PentaCore Laboratory, H-1094 Budapest, Bokréta u. 5, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Tobiás
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Korányi S. u. 2/a, Hungary.|PentaCore Laboratory, H-1094 Budapest, Bokréta u. 5, Hungary.
authors.forename: Karina
authors.initials: K
authors.lastname: Kató
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Korányi S. u. 2/a, Hungary.
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Kirschner
authors.affiliation: PentaCore Laboratory, H-1094 Budapest, Bokréta u. 5, Hungary.
authors.forename: Valéria
authors.initials: V
authors.lastname: Klujber
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Korányi S. u. 2/a, Hungary.|PentaCore Laboratory, H-1094 Budapest, Bokréta u. 5, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Lakatos
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Korányi S. u. 2/a, Hungary.|PentaCore Laboratory, H-1094 Budapest, Bokréta u. 5, Hungary.
authors.forename: János P
authors.initials: JP
authors.lastname: Kósa
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D018832:Molecular Chaperones; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D064828:Prolyl Hydroxylases; D011509:Proteoglycans / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C000716127:COL1A1 protein, human; C108053:CRTAP protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D011509:Proteoglycans; D064828:Prolyl Hydroxylases; C485657:P3H1 protein, human