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

• Published in: Frontiers in endocrinology (Lausanne) 2023-09, Vol.14, p.1149982-1149982
• Main Authors: Sałacińska, Kinga, Pinkier, Iwona, Rutkowska, Lena, Chlebna-Sokół, Danuta, Jakubowska-Pietkiewicz, Elżbieta, Michałus, Izabela, Kępczyński, Łukasz, Salachna, Dominik, Wieczorek-Cichecka, Nina, Piotrowicz, Małgorzata, Chilarska, Tatiana, Jamsheer, Aleksander, Matusik, Paweł, Wilk, Małgorzata, Petriczko, Elżbieta, Giżewska, Maria, Stecewicz, Iwona, Walczak, Mieczysław, Rybak-Krzyszkowska, Magda, Lewiński, Andrzej, Gach, Agnieszka
• Format: Article
• Language: English
• Subjects: COL1A1; COL1A2; collagen type I; connective tissue disorder; Endocrinology; next-generation sequencing; osteogenesis imperfecta
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2023.1149982

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.