CAJ | 학술논문

目的对一个马凡综合征家系进行FBN1基因突变筛查,探讨该家系的分子发病机制.方法在征得患者知情同意下,采集家系中四名患者及两名正常个体外周静脉血5毫升,提取基因组DNA.采用直接测序法对FBN1基因全部65个外显子,以及外显子内含子拼接部进行序列分析.Polyphen程序分析FBN1基因突变引起的蛋白结构和功能改变.结果通过基因突变筛查,发现该家系所有患者均携带有c.2261A＞G(p.Y754C)突变体,而患者家中正常个体及100名正常对照无此突变.经Polyphen程序分析,此突变将导致FBN1蛋白结构和功能的改变.结论 FBN1基因突变体p.Y754C是导致该马凡综合征家系的致病原因,此突变首次在中国马凡综合征患者中发现.
목적 대일개마범종합정가계진행FBN1기인돌변사사,탐토해가계적분자발병궤제.방법 재정득환자지정동의하,채집가계중사명환자급량명정상개체외주정맥혈5호승,제취기인조DNA.채용직접측서법대FBN1기인전부65개외현자,이급외현자내함자병접부진행서렬분석.Polyphen정서분석FBN1기인돌변인기적단백결구화공능개변.결과 통과기인돌변사사,발현해가계소유환자균휴대유c.2261A＞G(p.Y754C)돌변체,이환자가중정상개체급100명정상대조무차돌변.경Polyphen정서분석,차돌변장도치FBN1단백결구화공능적개변.결론 FBN1기인돌변체p.Y754C시도치해마범종합정가계적치병원인,차돌변수차재중국마범종합정환자중발현.
Objective To identify FBN1 gene mutations in a Chinese family with Marfan syndrome.Methods Four affected and two unaffected individuals in the family were recruited after informed consent.Five ml blood samples were drawn from each family member and genomic DNA was extracted. Mutations were detected by directly sequencing to the whole coding region and exon-intron boundaries of FBN1 gene.Polyphen program was used to predict the functional and structural changes of the mutant protein. Results We found all four affected individuals carried FBN1gene mutations, c. 2261A ＞ G ( p. Y754C), in exon18 by sequence analysis, while two unaffected family members and 100 normal controls did not have this mutation. A PSIC score of 2. 6 was acquired by Polyphen program analysis. Conclusion Our study supports that FBN1 gene mutation, c. 2261A ＞ G (p. Y754C), is the underlying molecular pathogenesis of this family with Marfan syndrome. This mutation is identified for the first time in Chinese population.