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目的 研究微纤维元基因 (FBN1 )突变引起的以心血管及眼部症状为主的家族性马凡综合征(Marfan’s syndrom e,MFS)的特点。方法 首先对 4代 (共计 5 0例 )家庭成员进行体检 ,筛选出有症状的个体及无症状的个体。采用单链构象分析 (SSCA)方法对 5 0例个体 FBN 1基因外显子进行筛选。在 FBN1基因的 6 5个外显子中 ,共计筛选了 2 1个外显子。在确定外显子 18SSCA异常后 ,对外显子 18的扩增标本进行直接突变检测。结果 按照最新诊断标准 2 6例被诊断患有 MFS。分子生物学检测发现这个家族中 FBN1基因外显子 18有 SSCA异常。结果显示所有临床上受累的个体都有同样形式的 SSCA异常 ,然而临床上无症状的个体及外姓配偶无一检出SSCA异常。在检测出 SSCA异常后 ,对先症者 (第一个发现患有 MFS的人 )及其患病的堂兄的外显子 18扩增片段 ,进行直接突变检测 ,发现外显子 75 4号密码子上半胱氨酸替代了酪氨酸 (Y75 4C)。结论 MFS为常染色体显性遗传。这个 MFS家族携带 FBN1突变 ,该突变导致以心血管及眼部症状为主的临床表现。临床拟表型各异 ,说明基因突变的表达受许多因素干扰。
Objective To study the characteristics of familial Marfan syndrome (MFS) caused by mutations of fibrillary meta-gene (FBN1) in cardiovascular and ocular conditions. Methods Four generations (total 50 cases) of family members were examined by physical examination, and the symptomatic individuals and asymptomatic individuals were screened out. Single-strand conformational analysis (SSCA) was used to screen exons of FBN 1 in 50 individuals. Of the 65 exons of the FBN1 gene, a total of 21 exons were screened. After confirming the abnormalities of exon 18SSCA, the exon 18 amplified samples were tested for direct mutation. Results According to the latest diagnostic criteria 26 cases were diagnosed with MFS. Molecular biology tests found that this family FBN1 gene exon 18 SSCA abnormalities. The results showed that all clinically affected individuals had the same form of SSCA abnormalities, whereas none of the clinically asymptomatic individuals and their surnames had an SSCA abnormality. After detection of an abnormality in SSCA, an exon 18 amplified fragment of the first symptom (the first person found to have MFS) and the cousin of his illness was subjected to direct mutation detection and found that exon 75 4 Cys on codon replaced tyrosine (Y75 4C). Conclusion MFS is autosomal dominant. This MFS family carries a mutation in FBN1 that leads to clinical manifestations characterized mainly by cardiovascular and ocular conditions. Different types of clinical phenotype, indicating that the expression of mutations affected by many factors.