Vanita Vanita, Singh Jai Rup, Singh Daljit, Varon Raymonda, Robinson Peter N, Sperling Karl
Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India.
Mol Vis. 2007 Oct 25;13:2035-40.
To identify the genetic defect in an autosomal dominant ectopia lentis (EL) family having 27 affected members in four generations.
Detailed family history and clinical data were recorded for 48 family members including 24 persons with isolated ectopia lentis. Candidate gene regions at 5q and 15q known to be linked with ectopia lentis were analyzed using fluorescent labeled microsatellite markers. Mutation screening in the candidate gene, fibrillin-1 (FBN1), at 15q was performed by bidirectional sequencing of the amplified products.
A maximum LOD score of 5.74 at theta=0.0 was obtained with marker D15S1024 in close proximity to FBN1 at 15q21. Mutation screening in FBN1 identified a C>T transition at nucleotide position c.718. This nucleotide change resulted in the substitution of highly conserved arginine by cysteine at codon 240 (R240C). This nucleotide substitution was not seen in any unaffected member of the family.
We report a recurrent R240C mutation in FBN1 in an autosomal dominant ectopia lentis family. This mutation has previously been reported in a family with isolated ectopia lentis, in another family with ectopia lentis and involvement of the skeleton and integument, and in one person with classic Marfan syndrome. This is the largest family with isolated ectopia lentis reported to date. The results of the present study provide convincing evidence for a correlation of R240C and isolated ectopia lentis. In addition, this is the first report of molecular characterization in an ectopia lentis family of Indian origin.
在一个四代中有27名受累成员的常染色体显性遗传性晶状体异位（EL）家系中确定基因缺陷。
记录了48名家庭成员的详细家族史和临床资料，其中包括24例单纯晶状体异位患者。使用荧光标记微卫星标记分析已知与晶状体异位相关的5号染色体和15号染色体上的候选基因区域。通过对扩增产物进行双向测序，对15号染色体上的候选基因原纤蛋白-1（FBN1）进行突变筛查。
在15q21靠近FBN1的标记D15S1024处，在θ=0.0时获得了最高LOD分数5.74。FBN1突变筛查在核苷酸位置c.718处发现了C>T转换。这种核苷酸变化导致密码子240处高度保守的精氨酸被半胱氨酸取代（R240C）。在该家系的任何未受累成员中均未发现这种核苷酸替代。
我们报告了一个常染色体显性遗传性晶状体异位家系中FBN1基因的复发性R240C突变。此前在一个单纯晶状体异位家系、另一个晶状体异位合并骨骼和皮肤受累的家系以及一名典型马凡综合征患者中报道过这种突变。这是迄今为止报道的最大的单纯晶状体异位家系。本研究结果为R240C与单纯晶状体异位之间的相关性提供了令人信服的证据。此外，这是关于印度裔晶状体异位家系分子特征的首次报道。
