Intractable Rare Dis Res. 2019;8(2):150-153. (DOI: 10.5582/irdr.2019.01046)

Splice receptor-site mutation c.697-2A>G of the COL1A1 gene in a Chinese family with osteogenesis imperfecta.

Zhai NX, Lu YQ, Wang YZ, Zhang SE, Peng CM, Zhang SS, Li TY, Chen M, Liu JL, Fang FL, Ren XZ, Han JX


Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and blue sclerae, which are mainly caused by a mutation of the COL1A1 or COL1A2 genes that encode type I procollagen. Mutations in the splice site of type I collagen genes are one of the mutations that cause OI and usually lead to a mild or moderate OI phenotype. A heterozygous A to G point mutation in intron 9 at the -2 position of the splice receptor site of COL1A1 was identified in a family with type I or IV OI. Three affected individuals in four generations of one family all presented with several clinical symptoms. They all had pectus carinatum, flat feet, gray-blue sclerae, and normal stature, teeth, hearing, and vision. Forearm fractures, small joint dislocations, and muscle weakness were all present in the patient's father and grandmother, who presented with a moderate type IV phenotype. The 10-year-old proband with type I OI had suffered a fracture twice, but had no history of joint dislocation or skin hyperextensibility. Charting the family helped to identify clinical symptoms in patients with mutations at the N-terminal of type I collagen genes.

KEYWORDS: Osteogenesis imperfecta, splice receptor-site mutation, COL1A1, N-terminal of type I collagen

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