在中国一个先天性白内障家族中鉴定出MIP基因的一种新型剪接位点突变。
Identification of a novel splice-site mutation in MIP in a Chinese congenital cataract family.
作者信息
Jiang Jin, Jin Chongfei, Wang Wei, Tang Xiajing, Shentu Xingchao, Wu Renyi, Wang Yao, Xia Kun, Yao Ke
机构信息
Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China.
出版信息
Mol Vis. 2009;15:38-44. Epub 2009 Jan 12.
PURPOSE
To map the locus and identify the gene causing autosomal dominant congenital cataract (ADCC) with "snail-like" phenotype in a large Chinese family.
METHODS
Clinical and ophthalmologic examinations were conducted on family members and documented by slit lamp photography. Linkage analysis was performed with an initial 41 microsatellite markers, then 3 additional markers flanking the major intrinsic protein (MIP) gene. Mutations were screened by DNA sequencing and verified by restriction fragment length polymorphism (RFLP) analysis.
RESULTS
Significant two-point LOD scores were obtained at 5 markers flanking MIP with the highest 3.08 (theta=0.00) at marker D12S1632. Mutation screening of MIP identified a heterozygous G>A transition at the acceptor splice site of intron 3 (IVS3 -1 G>A), abolishing a BstSF I restriction site in one allele of all the affected individuals.
CONCLUSIONS
We identified a novel splice-site mutation (IVS3 -1 G>A in MIP) in a Chinese ADCC family. To our knowledge, this is the first report on an acceptor splice-site mutation in human genes associated with ADCC.
目的
在一个大型中国家系中定位导致常染色体显性遗传性先天性白内障（ADCC）伴“蜗牛样”表型的基因座并鉴定相关基因。
方法
对家系成员进行临床和眼科检查，并用裂隙灯照相记录。首先使用41个微卫星标记进行连锁分析，然后对主要内在蛋白（MIP）基因侧翼的另外3个标记进行连锁分析。通过DNA测序筛选突变，并通过限制性片段长度多态性（RFLP）分析进行验证。
结果
在MIP侧翼的5个标记处获得了显著的两点连锁分析优势对数（LOD）分数，在标记D12S1632处最高为3.08（θ=0.00）。对MIP进行突变筛查，发现在所有受影响个体的一个等位基因中，内含子3的剪接受体位点（IVS3 -1 G>A）存在杂合性G>A转换，消除了一个BstSF I限制性位点。
结论
我们在中国一个ADCC家系中鉴定出一个新的剪接位点突变（MIP基因中的IVS3 -1 G>A）。据我们所知，这是关于人类基因中与ADCC相关的剪接受体位点突变的首次报道。
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