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NGS analysis of collagen type I genes in Polish patients with Osteogenesis imperfecta: a nationwide multicenter study

Authors :
Kinga Sałacińska
Iwona Pinkier
Lena Rutkowska
Danuta Chlebna-Sokół
Elżbieta Jakubowska-Pietkiewicz
Izabela Michałus
Łukasz Kępczyński
Dominik Salachna
Nina Wieczorek-Cichecka
Małgorzata Piotrowicz
Tatiana Chilarska
Aleksander Jamsheer
Paweł Matusik
Małgorzata Wilk
Elżbieta Petriczko
Maria Giżewska
Iwona Stecewicz
Mieczysław Walczak
Magda Rybak-Krzyszkowska
Andrzej Lewiński
Agnieszka Gach
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