Identification and In Vivo Functional Characterization of Novel Compound Heterozygous BMP1 Variants in Osteogenesis Imperfecta |
| |
| Authors: | Sung Yoon Cho P.V. Asharani Ok‐Hwa Kim Aritoshi Iida Noriko Miyake Naomichi Matsumoto Gen Nishimura Chang‐Seok Ki Geehay Hong Su Jin Kim Young Bae Sohn Sung Won Park Jieun Lee Younghee Kwun Thomas J. Carney Rimm Huh Shiro Ikegawa Dong‐Kyu Jin |
| |
| Affiliation: | 1. Department of Pediatrics, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;2. Institute of Molecular and Cell Biology, Proteos, Singapore;3. Department of Radiology Gachon University Gil Medical Center, Incheon, Republic of Korea;4. Laboratory for Bone and Joint Diseases, RIKEN Center for Integrated Medical Sciences, Tokyo, Japan;5. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan;6. Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan;7. Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;8. Department of Pediatrics, Kwandong University College of Medicine, Myongji Hospital, Goyang, Republic of Korea;9. Department of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Republic of Korea;10. Department of Pediatrics, Kwandong University College of Medicine, Cheil General Hospital and Woman's Health Care Center, Seoul, Republic of Korea;11. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore |
| |
| Abstract: | Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal‐dominant inheritance, but many autosomal‐recessive genes have been reported. We applied whole‐exome sequencing to identify mutations in a Korean OI patient who had an umbilical hernia, frequent fractures, a markedly short stature, delayed motor development, scoliosis, and dislocation of the radial head, with a bowed radius and ulna. We identified two novel variants in the BMP1 gene: c.808A>G and c.1297G>T. The former variant caused a missense change p.(Met270Val) and the latter variant caused the skipping of exon 10. The hypofunctional nature of the two variants was demonstrated in a zebrafish assay. |
| |
| Keywords: | osteogenesis imperfecta BMP1 zebrafish whole‐exome sequencing mutation |
|
|
