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目的 检测中国人马凡综合征 (Marfan syndrome,MFS)患者微纤维蛋白 1(fibrillin- 1,FBN1 )基因的突变及对马凡综合征患者的家系成员进行症状前诊断。方法 应用聚合酶链反应 -单链构象多态性技术和测序方法 ,对汉族 9个家系中共 17个 MFS患者进行基因突变检测 ;运用 FBN1 基因内 4个内含子中的可变串联重复序列构建染色体单倍型 ,进行家系单倍型连锁分析和基因诊断。结果 发现 MFS(A)家系 1 患者有单链构象改变 ,测序证实为位于 FBN1 基因第 2 5号外显子 32 4 3～ 32 5 6核苷酸之间有 1个 13bp的小片段缺失 ,为新位点基因移码突变 ,其序列为 gcctctgcaccca;单倍型连锁分析发现 MFS(B)家系 1 是 1个无症状期患者。结论 中国人 FBN1 基因突变可以引起马凡综合征 ,应用突变检测与单倍型连锁分析方法能为马凡综合征基因诊断提供依据
Objective To detect the mutation of fibrillin-1 (FBN1) gene in patients with Marfan syndrome (MFS) and to make a pre-symptomatic diagnosis of the family members of Marfan syndrome. METHODS: A total of 17 MFS patients from 9 pedigrees of Han were genotyped by polymerase chain reaction-single strand conformation polymorphism (PCR) and sequencing. The variable tandem repeats of four introns in FBN1 gene were constructed Chromosomal haplotypes, family linkage haplotype analysis and gene diagnosis. The results showed that there was a single-strand conformational change in the MFS (A) pedigree 1. The sequence was confirmed to be a 13 bp small fragment located between 3243 to 3256 nucleotides of exon 2 of FBN1 gene and was a new Site-directed frameshift mutation with the sequence of gcctctgcaccca. Haplotype linkage analysis revealed that MFS (B) family 1 was an asymptomatic patient. Conclusion Chinese FBN1 gene mutation can cause Marfan syndrome. Using mutation detection and haplotype linkage analysis can provide the basis for genetic diagnosis of Marfan syndrome