Hagstrom Stephanie A, Pauer Gayle J T, Reid Janet, Simpson Ellen, Crowe Sue, Maumenee Irene H, Traboulsi Elias I
Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Am J Med Genet A. 2005 Oct 1;138A(2):95-8. doi: 10.1002/ajmg.a.30803.
The SOX2 transcription factor is expressed early in the embryonic stem cells of the blastocyst and later in the neural stem cells. It is a member of the SOX family of proteins that carry a DNA-binding high-mobility group domain and additional domains that regulate embryonic development and cell fate determinations. We surveyed 93 patients with severe eye malformations for mutations in SOX2. Here, we report a novel nonsense mutation in one female patient with bilateral clinical anophthalmia, absence of all optic pathways, and other neurological abnormalities. The mutation, Q155X, creates a premature termination codon early in the transcriptional activation domain and is likely to be a null allele. Our data show that mutations in SOX2 can cause not only anophthalmia, but also aplasia of the optic nerve, chiasm and optic tract, as well as modest bilateral sensorineural hearing loss, and global developmental delay, underscoring the importance of SOX2 in early human eye and brain development.
SOX2转录因子在囊胚的胚胎干细胞中早期表达，随后在神经干细胞中表达。它是SOX蛋白家族的成员，该家族蛋白携带一个DNA结合高迁移率族结构域以及其他调节胚胎发育和细胞命运决定的结构域。我们对93例严重眼部畸形患者进行了SOX2突变检测。在此，我们报告一名患有双侧临床无眼症、所有视路缺失及其他神经学异常的女性患者存在一种新的无义突变。该突变Q155X在转录激活结构域早期产生一个提前终止密码子，很可能是一个无效等位基因。我们的数据表明，SOX2突变不仅可导致无眼症，还可引起视神经、视交叉和视束发育不全，以及轻度双侧感音神经性听力损失和全面发育迟缓，突显了SOX2在人类早期眼和脑发育中的重要性。
