Molekularno-genetička analiza osteogenesis imperfecta u kliničkoj praksi

Osteogenesis imperfecta (OI) is characterized by fractures with minimal or absent trauma, representing a continuum ranging from perinatal lethality through individuals with severe skeletal deformities to nearly asymptomatic individuals with mild predisposition to fractures. Diagnosis of OI is an interdisciplinary task based on family and/or patient history of fractures combined with characteristic physical fi ndings. Radiographic examination reveals fractures of varying ages and stages of healing, wormian bones, and osteopenia. As there is no defi nitive test for OI, molecular genetic testing by next generation sequencing (NGS) of COL1A1 and COL1A2 and up to 12 other genes is essential to confi rm the genetic background. Therefore, we designed a NGS gene panel comprising 12 genes involved in OI or severe osteoporosis. Here we report results in a cohort of 11 apparently sporadic young patients with OI, all off spring of unaff ected parents, who were referred to orthopaedic surgery at Sv. Katarina Special Hospital (Zabok/Zagreb, Croatia). Ten of these 11 patients could be classifi ed genetically. Overall, three genes with diff erent percent relating to the whole cohort were involved: COL1A1 (63.6%), COL1A2 (18.18%) and WNT1 (9.09%).Osteogenesis imperfecta (OI) je obilježena prijelomima uz minimalnu ili odsutnu traumu i predstavlja kontinuum u rasponu od perinatalne smrtnosti, osobe s teškim skeletnim deformitetima do gotovo asimptomatskih osoba s niskom sklonošću prijelomima. Dijagnosticiranje OI je interdisciplinski zadatak koji se temelji na obiteljskoj i/ili bolesnikovoj povijesti prijeloma u kombinaciji sa znakovitim fi zičkim nalazima. Radiografsko snimanje otkriva prijelome različite starosti i stadija zaraštanja, Wormove kosti i osteopeniju. Kako nema konačnog testa za OI, molekularno genetsko testiranje pomoću next generation sequencing (NGS) gena COL1A1 i COL1A2 te do 12 drugih gena bitno je za potvrdu genetske podloge. Stoga smo izradili NGS genski panel koji sadrži 12 gena uključenih u OI ili tešku osteoporozu. Prikazujemo rezultate dobivene u nizu od 11 očito sporadičnih mladih bolesnika s OI, svi potomci nezahvaćenih roditelja, koji su bili upućeni na ortopedsku kirurgiju u Specijalnoj bolnici sv. Katarina u Zaboku/Zagrebu. Deset od tih 11 bolesnika mogli smo genetski klasifi cirati. Sveukupno, uključena su bila tri gena u različitim postocima u našem nizu bolesnika: COL1A1 (63,6%), COL1A2 (18,18%) i WNT1 (9,09%)