Soria J M, Brito D, Barceló J, Fontcuberta J, Botero L, Maldonado J, Estivill X, Sala N
Molecular Genetics Department, Hospital Duran i Reynals, Barcelona, Spain.
Thromb Haemost. 1994 Jul;72(1):65-9.
Single strand conformation polymorphism (SSCP) analysis of exon 7 of the protein C gene has identified a novel splice site missense mutation (184, Q-->H), in a newborn child with purpura fulminans and undetectable protein C levels. The mutations, seen in the homozygous state in the child and in the heterozygous state in her mother, was characterized and found to be a G to C nucleotide substitution at the -1 position of the donor splice site of intron 7 of the protein C gene, which changes histidine 184 for glutamine (184, Q-->H). According to analysis of the normal and mutated sequences, this mutation should also abolish the function of the donor splice site of intron 7 of the protein C gene. Since such a mutation is compatible with the absence of gene product in plasma and since DNA sequencing of all protein C gene exons in this patient did not reveal any other mutation, we postulate that mutation 184, Q-->H results in the absence of protein C gene product in plasma, which could be the cause of the severe phenotype observed in this patient.
对一名患有暴发性紫癜且蛋白C水平检测不到的新生儿进行蛋白C基因第7外显子的单链构象多态性（SSCP）分析，发现了一种新的剪接位点错义突变（184，谷氨酰胺→组氨酸）。该突变在患儿中呈纯合状态，在其母亲中呈杂合状态，经鉴定为蛋白C基因第7内含子供体剪接位点-1位的G到C核苷酸替换，导致组氨酸184被谷氨酰胺取代（184，谷氨酰胺→组氨酸）。根据对正常序列和突变序列的分析，该突变也应消除蛋白C基因第7内含子供体剪接位点的功能。由于这种突变与血浆中基因产物的缺失相符，且该患者所有蛋白C基因外显子的DNA测序未发现任何其他突变，我们推测184，谷氨酰胺→组氨酸突变导致血浆中蛋白C基因产物缺失，这可能是该患者观察到的严重表型的原因。
