Lonero Antonella, Delvecchio Maurizio, Primignani Paola, Caputo Roberto, Bargiacchi Sara, Penco Silvana, Mauri Lucia, Andreucci Elena, Faienza Maria Felicia, Cavallo Luciano
J Pediatr Endocrinol Metab. 2016 May 1;29(5):603-5. doi: 10.1515/jpem-2015-0425.
OTX2 mutations are reported in patients with eye maldevelopment and in some cases with brain or pituitary abnormalities. We describe a child carrying a novel OTX2 heterozygous mutation. She presented microphthalmia, absence of retinal vascularization, vitreal spots and optic nerve hypoplasia in the right eye and mild macular dystrophy in the left eye. Midline brain structures and cerebral parenchyma were normal, except for the ectopic posterior pituitary gland. OTX2 sequencing showed a heterozygous c.402del mutation. Most of OTX2 mutations are nonsense or frameshift introducing a premature termination codon and resulting in a truncated protein. More rarely missense mutations occur. Our novel OTX2 mutation (c.402del) is a frameshift mutation (p.S135Lfs*43), never reported before, causing a premature codon stop 43 amino-acids downstream, which is predicted to generate a premature truncation. The mutation was associated with microphthalmia and ectopic posterior pituitary.
在眼部发育异常的患者以及某些伴有脑部或垂体异常的病例中，已报告存在OTX2突变。我们描述了一名携带新型OTX2杂合突变的儿童。她右眼表现为小眼症、视网膜无血管化、玻璃体斑点和视神经发育不全，左眼有轻度黄斑营养不良。除了垂体后叶异位外，中线脑结构和脑实质均正常。OTX2测序显示存在杂合的c.402del突变。大多数OTX2突变是无义或移码突变，会引入过早的终止密码子，导致蛋白质截短。错义突变则较为罕见。我们发现的新型OTX2突变（c.402del）是一种移码突变（p.S135Lfs*43），此前从未有过报道，它会在下游43个氨基酸处导致过早的密码子终止，预计会产生过早的截短。该突变与小眼症和垂体后叶异位有关。
