A novel variant of osteogenesis imperfecta type IV and low serum phosphorus level caused by a Val94Asp mutation in COL1A1

Yang,Qi; Xu,Hong; Luo,Jinsi; Zhang,Qinle; Xie,Bobo; Yi,Sheng; Rong,Xiuliang; Wang,Jin; Qin,Zailong; Jiang,Tingting; Lin,Li; Zuo,Yangjin; Fan,Xin

doi:10.3892/mmr.2018.8436

A novel variant of osteogenesis imperfecta type IV and low serum phosphorus level caused by a Val94Asp mutation in COL1A1

Authors:
- Qi Yang
- Hong Xu
- Jinsi Luo
- Qinle Zhang
- Bobo Xie
- Sheng Yi
- Xiuliang Rong
- Jin Wang
- Zailong Qin
- Tingting Jiang
- Li Lin
- Yangjin Zuo
- Xin Fan
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Affiliations: Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi 530023, P.R. China, Nanning Region Center for Disease Prevention and Control, Nanning, Guangxi 530023, P.R. China
Published online on: January 16, 2018 https://doi.org/10.3892/mmr.2018.8436
Pages: 4433-4439
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteogenesis imperfecta (OI) is a rare congenital disorder characterized by bone fragility and fractures, and associated with bone deformity, short stature, dentin, ligament and blue‑gray eye sclera. OI is caused by a heterozygous mutation in collagen α‑1(I) chain (COL1A1) or collagen α‑2(I) chain (COL1A2) genes that encode α chains of type I collagen. Collagen α chain peptide contains an N‑propeptide, which has a role in assembly and processing of collagen. Point mutations in the N‑propeptide domain appear to trigger OI. In the present study, a novel heterozygous missense mutation, c.281T>A (p.Val94Asp), was identified in the von Willebrand C domain of N‑terminal of type I collagen in an individual with type IV OI. The majority of N‑terminal mutations are associated with OI/Ehlers‑Danlos syndrome (EDS); however, in the present study, the affected individual did not suffer from EDS and the level of serum phosphorus of the patient was low (0.67 mmol/l). A number of clinical phenotypes were observed at the same variation site or in the same region on the polypeptide chain of COL1A, which suggests that additional genetic and environmental factors may influence the severity of OI. The present study may provide insight into the phenotype‑genotype association in collagen-associated diseases and improve clinical diagnosis of OI.

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