| 目的：利用中国Meesmann角膜营养不良（Meesmann’s Corneal Dystrophy, MCD）家系，通过连锁分析技术和基因定位技术对其进行分子遗传连锁分析，探讨该家系的致病相关基因。病例及方法：在临床上收集Meesmann角膜营养不良家系，包括三代患病者及正常人，通过详细的眼科检查，获得血液标本，提取基因组DNA，首先对已知基因KRT12 、KRT3周围标记物D17S800、D17S930、D12S390、D12S96分别进行基因扫描，对连锁区域内基因所有外显子PCR扩增产物进行直接测序。结果：该家系连锁的染色体微卫星标记物为D17S800和D17S930，lod=2.41 ((θ=0.00), 与KRT12基因连锁，所有外显子测序后发现该基因第一外显子（exon1）测序结果为第419编码子碱基突变T419A，编码的亮氨酸突变为组氨酸 L132H；结论：KRT12基因特异突变（T419A，L132H）是该中国人家系Meesmann角膜营养不良家族发病的分子基础。
关键词：Meesmann角膜营养不良；KRT12基因； 突变
A Novel Mutation on A Large Chinese Family with Meesmann’s Corneal Dystrophy WANG Le-jin*. *Peking University Eye Center /Peking University 3rd Hospital, Huazhong Science-Technology University, Academy of Life, Beijing 100083, China; ZHANG Qing-sheng*, *Xing Tai Eye Hospital, Hebe; TIAN xin, LIU Liang, Peking University Eye Center, Beijing;
* contributed equally to this work, co-first author.
Corresponding author: WANG Le-jin, E-mail:wanglj_puce@yahoo.com.cn
【Abstract】Objective: To investigate the muation of the KRT12 gene in affected members in a Large Chinese family with Meesmann’s Corneal Distrophy by molecular Genetics and Linkage analysis. Methods: Isolated the genome-DNA samples from the selected members in family, including the affected and unaffected members. Mapping the locus of Molecular Genetics used the selected Markers(D17S800、D17S930、D12S390、D12S96) in the locus around identified genes (KRT12, KRT3), if linked with one of them, PCR the exons of gene, and sequencing them directly. All the members were examined with slit lamp biomicroscope and photographed. 100 normal subjects were recruited by mutational analysis as controls. Results: Molecular Genetics and linkage analysis to map the gene, linked with D17S800 and D17S930, lod=2.41 ((θ=0.00) ,identified the KRT12 gene in that region. KRT12 gene sequences of affected members show the mutant in Exon 1, T419A, L132H, all the affected members were heterozygous, none of them in unaffected and other 100 normal controls. The clinical appearance in all affected members were diagnosed as Meesmann’s corneal dystrophy. Conclusion: It is the molecular mechanism of Meesmann’s Corneal Dystrophy in a large Chinese family that mutant of KRT12 in exon 1, T419A, L132H.
【Key word】: Meesmann’s Corneal Dystrophy; KRT12; mutation
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