title: Heterozygous mutation of c.3521C>T in COL1A1 may cause mild osteogenesis imperfecta/Ehlers-Danlos syndrome in a Chinese family.
abstract: Osteogenesis imperfecta (OI) is an inheritable connective tissue disorder with a broad clinical heterozygosis, which can be complicated by other connective tissue disorders like Ehlers-Danlos syndrome (EDS). OI/EDS are rarely documented. Most OI/EDS mutations are located in the N-anchor region of type I procollagen and predominated by glycine substitution. We identified a c.3521C>T (p.A1174V) heterozygous mutation in COL1A1 gene in a four-generation pedigree with proposed mild OI/EDS phenotype. The affected individuals had blue sclera and dentinogenesis imperfecta (DI) was uniformly absent. The OI phenotype varied from mild to moderate, with the absence of scoliosis and increased skin extensibility. Easy bruising, joint dislocations and high Beighton score were present in some affected individuals. EDS phenotype is either mild or unremarkable in some individuals. The mutation is poorly conserved and in silico prediction support the relatively mild phenotype. The molecular mechanisms of the mutation that leads to the possible OI/EDS phenotype should be further identified by biochemical analysis of N-propeptide processing and steady state collagen analysis.
authors: Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Laboratory for Virology of Shandong Province, Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, Ji'nan, China; ; School of Medicine and Life Sciences, University of Ji'nan-Shandong Academy of Medical Sciences, Ji'nan, China;
authors: Xianlong
authors: X
authors: Shi
authors: Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Laboratory for Virology of Shandong Province, Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, Ji'nan, China; ; School of Medicine and Life Sciences, University of Ji'nan-Shandong Academy of Medical Sciences, Ji'nan, China;
authors: Yanqin
authors: Y
authors: Lu
authors: Department of Paediatric Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, China;
authors: Yanzhou
authors: Y
authors: Wang
authors: Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Laboratory for Virology of Shandong Province, Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, Ji'nan, China; ; School of Medicine and Life Sciences, University of Ji'nan-Shandong Academy of Medical Sciences, Ji'nan, China;
authors: Yu-Ang
authors: YA
authors: Zhang
authors: Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Laboratory for Virology of Shandong Province, Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, Ji'nan, China; ; School of Medicine and Life Sciences, University of Ji'nan-Shandong Academy of Medical Sciences, Ji'nan, China;
authors: Yuanwei
authors: Y
authors: Teng
authors: Department of Orthopaedic Surgery, The People's Hospital of Wuqing District, Tianjin, China.
authors: Wanshui
authors: W
authors: Han
authors: Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Laboratory for Virology of Shandong Province, Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, Ji'nan, China; ; School of Medicine and Life Sciences, University of Ji'nan-Shandong Academy of Medical Sciences, Ji'nan, China;
authors: Zhenzhong
authors: Z
authors: Han
authors: Department of Paediatric Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, China;
authors: Tianyou
authors: T
authors: Li
authors: Department of Orthopaedic Surgery, The People's Hospital of Wuqing District, Tianjin, China.
authors: Mei
authors: M
authors: Chen
authors: Department of Orthopaedic Surgery, The People's Hospital of Wuqing District, Tianjin, China.
authors: Junlong
authors: J
authors: Liu
authors: Department of Orthopaedic Surgery, The People's Hospital of Wuqing District, Tianjin, China.
authors: Fengling
authors: F
authors: Fang
authors: Department of Orthopaedic Surgery, The People's Hospital of Wuqing District, Tianjin, China.
authors: Conghui
authors: C
authors: Dou
authors: Department of Orthopaedic Surgery, The People's Hospital of Wuqing District, Tianjin, China.
authors: Xiuzhi
authors: X
authors: Ren
authors: Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Laboratory for Virology of Shandong Province, Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, Ji'nan, China; ; School of Medicine and Life Sciences, University of Ji'nan-Shandong Academy of Medical Sciences, Ji'nan, China;
authors: Jinxiang
authors: J
authors: Han
keywords: Ehlers-Danlos syndrome; Osteogenesis imperfecta; in silico prediction; mutations; type I collagen