Winterpacht A, Hilbert M, Schwarze U, Mundlos S, Spranger J, Zabel B
Children's Hospital, University of Mainz, Germany.
Hum Mutat. 1994;4(4):257-62. doi: 10.1002/humu.1380040405.
Osteoarthrosis represents a very common disease with heterogeneous etiology. In some pedigrees linkage of the condition with the type II collagen gene (COL2A1) has been established, but information on the underlying gene defect is still incomplete as only one mutation causing this phenotype has been identified. We analyzed the COL2A1 gene in a 27-year-old woman and her 47-year-old mother presenting with severe premature osteoarthrosis and X-ray signs compatible with mild spondyloepiphyseal dysplasia. Examination of the complete gene in both patients was done by amplification of all 54 exons, screening of the PCR products by SSCP-analysis, and subsequent sequencing. In mother and daughter a G to A transition at the 5'-end of exon 21 was detected, leading to a substitution of serine for glycine at position 274 of the triple helical domain. The mutation was not present in unaffected family members or in healthy control individuals. The autosomal dominant spondylarthropathies may represent the less severe entities of the clinical spectrum of type II collagenopathies.
骨关节炎是一种病因多样的常见疾病。在一些家系中,已确定该病与II型胶原基因(COL2A1)存在连锁关系,但由于仅鉴定出一种导致该表型的突变,关于潜在基因缺陷的信息仍不完整。我们分析了一名27岁女性及其47岁母亲的COL2A1基因,她们患有严重的早发性骨关节炎,且X线表现与轻度脊椎骨骺发育不良相符。通过扩增所有54个外显子、利用单链构象多态性分析(SSCP分析)筛选PCR产物并随后进行测序,对两名患者的整个基因进行了检测。在母亲和女儿中,检测到外显子21 5'端的G到A转换,导致三螺旋结构域第274位的丝氨酸取代了甘氨酸。未患病的家庭成员或健康对照个体中不存在该突变。常染色体显性脊椎关节病可能代表II型胶原病临床谱中较轻的类型。