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目的 在白人群体中 ,导致人类补体第 8成份 β亚基缺陷的分子基础主要是在编码 β亚基基因的第 9外显子上发生碱基 C→ T的突变 ,从而形成终止密码 ,导致 C8β亚基不能完全合成。国外学者在两例 C8β亚基完全缺失的患者家系研究中 ,发现这两例β亚基缺失个体只是第 9外显子上碱基 C→ T突变的杂合子 ,现进一步寻找这两例 C8β亚基完全缺失的分子遗传学机理。方法 对两例 C8β亚基完全缺失患者的 C8β编码基因的全部 11个外显子的 PCR扩增产物进行 DNA测序分析并与正常人 DNA序列进行对比。结果 两例完全性 C8β亚基缺失患者的蛋白质编码基因中 ,分别在第 3外显子的 2 98和 388位置发现了 C→T突变 ,同时对这两个突变位点的家系分析也证实 ,位于第 3外显子上的这两个突变位点是独立于第 9外显子的突变而遗传。结论 所发现的两个突变位点均能形成终止密码而导致 C8β亚基合成提前终止 ,因此这两例患者 C8β亚基完全缺失的分子遗传学机理是由于编码 C8β亚基的基因在第 3和第 9外显子上同时发生了点突变 ,进而形成终止密码造成 C8β亚基合成终止所致。
Purpose In the white population, the molecular basis leading to defects in the β subunit of human complement 8 component is primarily the mutation of the C → T base on the 9th exon encoding the β subunit gene, resulting in a stop codon leading to the formation of C8β Subunits can not be completely synthesized. Foreign scholars in two cases of complete deletion of C8β subunit in patients with pedigree studies found that these two cases of β subunit deletion is only exon 9 on the base of C → T mutation of heterozygous, and now look for these two cases of C8β sub The complete absence of molecular basis of molecular genetics. Methods PCR amplification products of all 11 exons of C8β coding gene in two patients with complete deletion of C8β subunit were analyzed by DNA sequencing and compared with normal human DNA sequences. Results Two cases of complete deletion of C8β subunit in patients with protein-coding genes found in exon 3 of 988 and 388 position of the C → T mutation at the same time the two mutation sites of family analysis also confirmed that, These two mutations located on exon 3 are inherited independently of the mutation at exon 9. CONCLUSION: The found two stop codons resulted in the early termination of the synthesis of C8β subunits. Therefore, the molecular genetic mechanism of the complete deletion of the C8β subunit in the two cases is due to the fact that the gene encoding C8β isoform Exon 9 at the same time point mutations occurred, and then the formation of a stop codon caused by the synthesis of C8β subunit termination.