Williams C J, Considine E L, Knowlton R G, Reginato A, Neumann G, Harrison D, Buxton P, Jimenez S, Prockop D J
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107.
Hum Genet. 1993 Nov;92(5):499-505. doi: 10.1007/BF00216458.
Direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA from a patient with spondyloepiphyseal dysplasia and precocious osteoarthritis revealed a single-base change in exon 11 of the type II procollagen gene (COL2A1), which produces an Arg-->Cys mutation in one allele. The proband is a member of a large Chilean kindred presenting with chondrodysplasia of the hips, knees, shoulders, elbows, and spine associated with severe, early-onset osteoarthritis. All affected individuals exhibit mildly short stature; in addition, five out of seven affected family members display shortened metacarpals or metatarsals. DNA from affected and unaffected family members was PCR-amplified and analysis of restriction digests of the products determined that the mutation segregated with the disease with a lod score of 2.2 at zero recombination. The mutation, which resides in the triple-helical region of type II procollagen at amino acid position 75, is the second example of an Arg-->Cys mutation in the COL2A1 gene in heritable cartilaginous disease and is the first example of a point mutation in the amino terminal region of the alpha 1(II) chain, that results in a spondyloepiphyseal dysplastic phenotype.
对一名患有脊椎骨骺发育不良和早熟性骨关节炎患者的聚合酶链反应（PCR）扩增基因组DNA进行直接测序，发现II型前胶原基因（COL2A1）第11外显子有一个单碱基变化，导致一个等位基因发生精氨酸→半胱氨酸突变。先证者是一个智利大家族的成员，该家族成员表现为髋、膝、肩、肘和脊柱软骨发育不良，并伴有严重的早发性骨关节炎。所有受影响个体均有轻度身材矮小；此外，7名受影响家庭成员中有5人掌骨或跖骨缩短。对受影响和未受影响家庭成员的DNA进行PCR扩增，并对产物的限制性酶切分析确定该突变与疾病共分离，在零重组时连锁值为2.2。该突变位于II型前胶原三螺旋区域的第75位氨基酸处，是遗传性软骨疾病中COL2A1基因精氨酸→半胱氨酸突变的第二个例子，也是α1（II）链氨基末端区域点突变导致脊椎骨骺发育不良表型的第一个例子。
