Cole W G, Chan D, Chambers G W, Walker I D, Bateman J F
J Biol Chem. 1986 Apr 25;261(12):5496-503.
A child with the type VII form of the Ehlers-Danlos syndrome was shown to have a structural defect in the amino terminus of the pro-alpha 1(I) chain of type I procollagen. Normal and mutant amino-terminal cyanogen bromide peptides (pN-alpha 1(I) CB0,1 peptides) were purified from the medium of the patient's cultured fibroblasts. Amino acid sequencing of tryptic peptides derived from the mutant pN-alpha 1(I) CB0,1 peptide showed that an expected sequence of 24 amino acids (positions 136-159 of the normal pN-alpha 1(I) CB0,1 peptide) was deleted. The segment deleted from the mutant pro-alpha 1(I) chain contains the small globular region of the NH2-propeptide, the procollagen N-proteinase cleavage site, the NH2-telopeptide, and first triplet of the helix of the alpha I(I) collagen chain (Chu, M.-L., de Wet, W., Bernard, M., Ding, J.F., Morabito, M., Myers, J., Williams, C., and Ramirez, F. (1984) Nature 310, 337-340). Loss of the procollagen N-proteinase cleavage site from the mutant pro-alpha 1(I) chain accounted for the persistence of its NH2-propeptide despite normal production of the N-proteinase by cultured mutant fibroblasts. Collagen production by mutant fibroblasts was doubled possibly due to reduced feedback inhibition by the NH2-propeptides. The child appeared to be heterozygous for the peptide deletion and, as the parents did not show any evidence of the deletion, it is likely that the child had a new mutation of one allele of the pro-alpha 1(I) gene. The deleted peptide corresponds precisely to the sequence coded by exon 46 of the normal pro-alpha 1(I) gene (Chu, M.-L., de Wet, W., Bernard, M., Ding, J.F., Morabito, M., Myers, J., Williams, C., and Ramirez, F. (1984) Nature 310, 337-340).
一名患有VII型埃勒斯-当洛综合征的儿童被证明其I型前胶原的前α1（I）链氨基末端存在结构缺陷。从该患者培养的成纤维细胞培养基中纯化出正常和突变的氨基末端溴化氰肽（pN-α1（I）CB0,1肽）。对源自突变pN-α1（I）CB0,1肽的胰蛋白酶肽进行氨基酸测序表明，正常pN-α1（I）CB0,1肽预期的24个氨基酸序列（位置136 - 159）缺失。从突变前α1（I）链中缺失的片段包含NH2 - 前肽的小球形区域、前胶原N蛋白酶切割位点、NH2 - 端肽以及αI（I）胶原链螺旋的第一个三联体（朱，M.-L.，德韦特，W.，伯纳德，M.，丁，J.F.，莫拉比托，M.，迈尔斯，J.，威廉姆斯，C.，和拉米雷斯，F.（1984年）《自然》310，337 - 340）。尽管培养的突变成纤维细胞正常产生N蛋白酶，但突变前α1（I）链中前胶原N蛋白酶切割位点的缺失导致其NH2 - 前肽持续存在。突变成纤维细胞的胶原蛋白产生量增加了一倍，这可能是由于NH2 - 前肽的反馈抑制作用降低所致。该儿童似乎是肽缺失的杂合子，由于其父母未显示出任何缺失的证据，很可能该儿童的前α1（I）基因的一个等位基因发生了新的突变。缺失的肽与正常前α1（I）基因第46外显子编码的序列精确对应（朱，M.-L.，德韦特，W.，伯纳德，M.，丁，J.F.，莫拉比托，M.，迈尔斯，J.，威廉姆斯，C.，和拉米雷斯，F.（1984年）《自然》310，337 - 340）。
