Yang Huiqin, Xiao Xueshan, Li Shiqiang, Mai Guiying, Zhang Qingjiong
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, PR China.
Mol Vis. 2011 Apr 29;17:1128-35.
Mutations in tetraspanin 12 (TSPAN12) have recently been identified as a cause of autosomal dominant familial exudative vitreoretinopathy (FEVR). The purpose of this study was to detect TSPAN12 mutations in Chinese patients with FEVR and to describe the associated phenotypes.
Sanger sequencing was used to analyze the seven coding exons and their adjacent regions of TSPAN12 in 49 unrelated FEVR patients. Clinical phenotypes of the patients with TSPAN12 mutations were documented.
Three novel heterozygous mutations in TSPAN12 were identified in three patients from unrelated families: c.146C>T (p.Thr49Met), c.313T>C (p.Cys105Arg), and c.601delC (p.Leu201PhefsX14). All three mutations involved highly conserved residues and were not present in 180 normal individuals. Ocular phenotypes included retinal folds, inferotemporal dragging of the optic disc and macula, increased vessels in the equatorial region, and a peripheral avascular zone. A father and his daughter had the same mutation but the father only had mild peripheral fundus changes while his daughter had obvious dragged disc and macular ectopia.
Our results suggest that TSPAN12 mutations are responsible for FEVR. Similar to patients with mutations in NDP, LRP5, or FZD4, the phenotypes associated with TSPAN12 mutations showed great variations between different individuals within a family and between the two eyes in individual patients.
四跨膜蛋白12（TSPAN12）突变最近被确定为常染色体显性遗传性家族性渗出性玻璃体视网膜病变（FEVR）的病因。本研究的目的是检测中国FEVR患者中的TSPAN12突变，并描述相关表型。
采用桑格测序法分析49例无亲缘关系的FEVR患者中TSPAN12的7个编码外显子及其相邻区域。记录TSPAN12突变患者的临床表型。
在来自无亲缘关系家族的3例患者中鉴定出3种TSPAN12的新型杂合突变：c.146C>T（p.Thr49Met）、c.313T>C（p.Cys105Arg）和c.601delC（p.Leu201PhefsX14）。所有这3种突变均涉及高度保守的残基，且在180名正常个体中不存在。眼部表型包括视网膜皱褶、视盘和黄斑颞下移位、赤道区域血管增多以及周边无血管区。一名父亲和他的女儿有相同的突变，但父亲仅有轻度周边眼底改变，而他的女儿有明显的视盘移位和黄斑异位。
我们的结果表明TSPAN12突变是FEVR的病因。与NDP、LRP5或FZD4突变患者相似TSPAN12突变相关的表型在家族内不同个体之间以及个体患者的双眼之间表现出很大差异。
