Cristina Gug1, Lavinia Caba2, Ioana Mozos3, Dana Stoian4, Diter Atasie5, Miruna Gug6, Eusebiu Vlad Gorduza7. 1. Department of Microscopic Morphology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. Electronic address: dr.cristina.gug@gmail.com. 2. Department 8 - Medicine of Mother and Child "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania. Electronic address: lavinia_zanet@yahoo.com. 3. Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania; Center for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. Electronic address: ioana_mozos@yahoo.com. 4. 2nd Department of Internal Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. Electronic address: stoian.dana@umft.ro. 5. Department of Clinical Medicine, Faculty of Medicine, "Lucian Blaga" University, Sibiu, Romania. Electronic address: diter_ro@yahoo.com. 6. "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. Electronic address: miruna.gug@gmail.com. 7. Department 8 - Medicine of Mother and Child "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania. Electronic address: vgord@mail.com.
Abstract
BACKGROUND: Osteogenesis imperfecta (OI) is a rare disease characterized by increased bone fragility and predisposition to fractures, bone deformities and other major signs such as dentinogenesis imperfecta, blue sclera and deafness. Over 90% of OI cases are caused by mutations in the COL1A1 and COL1A2 genes and the inheritance is autosomal dominant. METHODS: We present a case of a couple requesting genetic counseling, because the man was diagnosed with OI on a clinical and radiological basis and the woman was pregnant. Whole exomes sequencing (WES) was performed in order to identify the mutation (s), followed by prenatal diagnosis. RESULTS: WES identified a rare splicing mutation c.1155+1G>C in the COL1A1 gene recognized to be pathogenic and subsequently confirmed by next generation sequencing. The carrier state of the mutation was excluded for the fetus, so the pregnancy was further pursued and a healthy baby was born at term. CONCLUSIONS: WES is a new and effective technique for detecting pathogenic variants in monogenic diseases and it is preferable to use such a technique in diseases with genetic heterogeneity especially when time does not allow another time-consuming diagnostic technique such classical Sanger sequencing. WES offers possibility to expand the global spectrum of OI pathogenic variants enabling the diagnosis of the disease.
BACKGROUND:Osteogenesis imperfecta (OI) is a rare disease characterized by increased bone fragility and predisposition to fractures, bone deformities and other major signs such as dentinogenesis imperfecta, blue sclera and deafness. Over 90% of OI cases are caused by mutations in the COL1A1 and COL1A2 genes and the inheritance is autosomal dominant. METHODS: We present a case of a couple requesting genetic counseling, because the man was diagnosed with OI on a clinical and radiological basis and the woman was pregnant. Whole exomes sequencing (WES) was performed in order to identify the mutation (s), followed by prenatal diagnosis. RESULTS: WES identified a rare splicing mutation c.1155+1G>C in the COL1A1 gene recognized to be pathogenic and subsequently confirmed by next generation sequencing. The carrier state of the mutation was excluded for the fetus, so the pregnancy was further pursued and a healthy baby was born at term. CONCLUSIONS: WES is a new and effective technique for detecting pathogenic variants in monogenic diseases and it is preferable to use such a technique in diseases with genetic heterogeneity especially when time does not allow another time-consuming diagnostic technique such classical Sanger sequencing. WES offers possibility to expand the global spectrum of OI pathogenic variants enabling the diagnosis of the disease.
Authors: Nelimar Cruz-Centeno; Jean F Saenz-Maisonet; Paola M López-Dones; Alberto Santiago-Cornier; Victor N Ortiz-Justiniano Journal: Am J Case Rep Date: 2022-05-18