Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice
| Autor: | Gyöngyi Kirschner, Peter Horvath, Karina Kató, Bálint Tobiás, János P. Kósa, Valéria Klujber, Kristóf Árvai, Peter L. Lakatos, Bernadett Balla |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent Sequence analysis Disease Biology Polymorphism Single Nucleotide Collagen Type I Prolyl Hydroxylases Article DNA sequencing 03 medical and health sciences 0302 clinical medicine Bone Density Polymorphism (computer science) medicine Humans Child Gene Genetics Extracellular Matrix Proteins Membrane Glycoproteins Multidisciplinary High-Throughput Nucleotide Sequencing Infant Sequence Analysis DNA Ion semiconductor sequencing Osteogenesis Imperfecta medicine.disease Stop codon Collagen Type I alpha 1 Chain 030104 developmental biology Osteogenesis imperfecta Child Preschool 030220 oncology & carcinogenesis Female Proteoglycans Molecular Chaperones |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep28417 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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