Reis Linda M, Khan Ayesha, Kariminejad Ariana, Ebadi Farhad, Tyler Rebecca C, Semina Elena V
Department of Pediatrics and Children’s Research Institute at the Medical College of Wisconsin, Children’s Hospital of Wisconsin, Milwaukee, WI, USA.
Mol Vis. 2011;17:2527-32. Epub 2011 Sep 28.
To further explore the spectrum of mutations in the Visual System Homeobox 2 (VSX2/CHX10) gene previously found to be associated with autosomal recessive microphthalmia.
We screened 95 probands with syndromic or isolated developmental ocular conditions (including 55 with anophthalmia/microphthalmia) for mutations in VSX2.
Homozygous mutations in VSX2 were identified in two out of five consanguineous families with isolated microphthalmia. A novel missense mutation, c.668G>C (p.G223A), was identified in a large Pakistani family with multiple sibships affected with bilateral microphthalmia. This p.G223A mutation affects the conserved CVC motif that was shown to be important for DNA binding and repression activities of VSX2. The second mutation, c.249delG (p.Leu84SerfsX57), was identified in an Iranian family with microphthalmia; this mutation has been previously reported and is predicted to generate a severely truncated mutant protein completely lacking the VSX2 homeodomain, CVC domain and COOH-terminal regions.
Mutations in VSX2 represent an important cause of autosomal recessive microphthalmia in consanguineous pedigrees. Identification of a second missense mutation in the CVC motif emphasizes the importance of this region for normal VSX2 function.
进一步探究先前发现与常染色体隐性小眼症相关的视觉系统同源盒2（VSX2/CHX10）基因的突变谱。
我们对95名患有综合征性或孤立性发育性眼部疾病的先证者（包括55名无眼症/小眼症患者）进行了VSX2基因突变筛查。
在5个患有孤立性小眼症的近亲家庭中，有2个家庭鉴定出VSX2纯合突变。在一个有多个患病同胞患双侧小眼症的大型巴基斯坦家庭中，鉴定出一个新的错义突变，即c.668G>C（p.G223A）。这个p.G223A突变影响了保守的CVC基序，该基序对VSX2的DNA结合和抑制活性很重要。第二个突变，c.249delG（p.Leu84SerfsX57），在一个患有小眼症的伊朗家庭中被鉴定出来；这个突变先前已有报道，预计会产生一个严重截短的突变蛋白，完全缺乏VSX2同源结构域、CVC结构域和COOH末端区域。
VSX2基因突变是近亲家系中常染色体隐性小眼症的一个重要原因。在CVC基序中鉴定出第二个错义突变，强调了该区域对VSX2正常功能的重要性。
