Novel FBN1 mutations associated with predominant ectopia lentis and marfanoid habitus in Chinese patients.
Novel FBN1 mutations associated with predominant ectopia lentis and marfanoid habitus in Chinese patients.
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DOI：
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发表时间：
2007-07
期刊：
影响因子：
2.2
通讯作者：
C. Jin;K. Yao;Jin Jiang;Xiajing Tang;X. Shentu;Renyi Wu
中科院分区：
文献类型：
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作者：
C. Jin;K. Yao;Jin Jiang;Xiajing Tang;X. Shentu;Renyi Wu
目的研究中国人以异位晶状体(EL)为主的马凡氏习惯症患者的纤维蛋白-1基因(FBN1)突变情况，为进一步研究其基因-表型相关性提供依据。方法对来自7个中国家庭的患者进行全面的体格、眼科和心血管检查。从患者外周血白细胞中提取基因组DNA。通过聚合酶链式反应(PCR)扩增FBN1基因的65个外显子和侧翼内含子序列，并通过DNA直接测序进行突变筛查。结果在FBN1基因中发现了3个新的突变，即外显子2的c.203G和gt；T、外显子5的c.502T和gt；C、外显子16的c.2096G和gt；C，以及4个已知突变：外显子4的c.364C和gt；T、外显子13的c.1633C和gt；T、外显子15的c.1879C和gt；T、外显子37的c.4588C和gt；T。结论我们在FBN1基因中发现了3个新突变和4个已知突变，并发现半胱氨酸替代与EL高度相关。这些结果扩大了FBN1的突变谱，丰富了我们对FBN1突变所致的基因型-表型相关性的知识。据我们所知，这是纤维蛋白-1独特的NH2-末端结构域中半胱氨酸残基丢失的第一个报告。
PURPOSE To identify mutations in the fibrillin-1 gene (FBN1) and provide further information about genotype-phenotype correlations in Chinese patients with predominant ectopia lentis (EL) and marfanoid habitus. METHODS Patients from seven Chinese families underwent complete physical, ophthalmic, and cardiovascular examination. Genomic DNA was extracted from leukocytes of peripheral blood from the patients. The 65 exons and flanking intronic sequences of FBN1 were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. RESULTS Three novel mutations, c.203G>T in exon 2, c.502T>C in exon 5, and c.2096G>C in exon 16 as well as four known mutations, c.364C>T in exon 4, c.1633C>T in exon 13, c.1879C>T in exon 15, and c.4588C>T in exon37, were identified in FBN1. CONCLUSIONS We identified three novel mutations and four known mutations in FBN1 and found cysteine substitution highly related to EL. These results expand the mutation spectrum in FBN1 and enrich our knowledge of genotype-phenotype correlations due to FBN1 mutations. To our knowledge, this is the first report of cysteine residue loss in the unique NH2-terminal domain of fibrillin-1.