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NGS analysis of collagen type I genes in Polish patients with Osteogenesis imperfecta: a nationwide multicenter study
- Source :
- Frontiers in Endocrinology, Vol 14 (2023)
- Publication Year :
- 2023
- Publisher :
- Frontiers Media S.A., 2023.
-
Abstract
- Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue. It presents with a wide spectrum of skeletal and extraskeletal features, and ranges in severity from mild to perinatal lethal. The disease is characterized by a heterogeneous genetic background, where approximately 85%–90% of cases have dominantly inherited heterozygous pathogenic variants located in the COL1A1 and COL1A2 genes. This paper presents the results of the first nationwide study, performed on a large cohort of 197 Polish OI patients. Variants were identified using a next-generation sequencing (NGS) custom gene panel and multiplex ligation probe amplification (MLPA) assay. The following OI types were observed: 1 (42%), 2 (3%), 3 (35%), and 4 (20%). Collagen type I pathogenic variants were reported in 108 families. Alterations were observed in α1 and α2 in 70% and 30% of cases, respectively. The presented paper reports 97 distinct causative variants and expands the OI database with 38 novel pathogenic changes. It also enabled the identification of the first glycine-to-tryptophan substitution in the COL1A1 gene and brought new insights into the clinical severity associated with variants localized in “lethal regions”. Our results contribute to a better understanding of the clinical and genetic aspects of OI.
Details
- Language :
- English
- ISSN :
- 16642392
- Volume :
- 14
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f46f73cf625d46ddb2885a7702d86c5c
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fendo.2023.1149982