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.
摘要：
成骨不全症（OI）是一种罕见的先天性疾病，以骨脆性和骨折为特征，并与骨畸形有关，身材矮小,牙本质,韧带和蓝灰色眼睛巩膜。OI是由编码I型胶原蛋白α链的胶原蛋白α-1（I）链（COL1A1）或胶原蛋白α-2（I）链（COL1A2）基因中的杂合突变引起的。胶原α链肽含有N-前肽，在胶原蛋白的组装和加工中起作用。N-前肽结构域中的点突变似乎触发了OI。在本研究中,一种新的杂合错义突变,c.281T>A（p。Val94Asp),在IV型OI个体的I型胶原蛋白N末端的vonWillebrandC结构域中鉴定。大多数N端突变与OI/Ehlers‑Danlos综合征（EDS）相关；然而，在本研究中，受影响的个体没有EDS，患者的血清磷水平较低（0.67mmol/l）。在COL1A的多肽链上的相同变异位点或相同区域观察到许多临床表型，这表明额外的遗传和环境因素可能会影响OI的严重程度。本研究可能提供对胶原相关疾病中表型与基因型关联的见解，并改善OI的临床诊断。
