Henderson Robert H, Williamson Kathleen A, Kennedy Joanna S, Webster Andrew R, Holder Graham E, Robson Anthony G, FitzPatrick David R, van Heyningen Veronica, Moore Anthony T
Moorfields Eye Hospital, London, United Kingdom.
Mol Vis. 2009 Nov 21;15:2442-7.
To describe the clinical findings of a patient with an early onset retinal dystrophy and a novel mutation in OTX2, and to compare these findings with previously reported cases.
Using direct sequencing, we screened 142 patients, who had either Leber congenital amaurosis (LCA) or early onset retinal dystrophy (EORD), for mutations in OTX2. All patients received a detailed ophthalmic examination including electroretinography and retinal imaging.
Only one mutation in OTX2 was identified. A novel heterozygous p.S138X stop mutation was identified in a seven-year-old male who had an infantile onset retinal dystrophy. The mutation was not present in either parent or in 181 blood donor samples. There was a history of failure to thrive in infancy, poor feeding, and growth hormone deficiency. Poor vision and nyctalopia was present from the first year. Funduscopy revealed a hyperpigmented peripapillary ring with a fine granular pigmentation of the RPE throughout the fundus. The scotopic bright flash ERG a-wave was subnormal and the waveform electronegative, in keeping with dysfunction both at the level of the photoreceptor and post-phototransduction. Visual function has been stable to date.
Mutations in OTX2 have been reported in association with major developmental malformations of the eye, with retinal dystrophies such as LCA, and with pituitary dysfunction and seizure activity in some cases. This case adds further support for a role of OTX2 both in retinal development and pituitary function, and highlights a novel retinal dystrophy phenotype seen in association with mutations in OTX2.
描述一名患有早发性视网膜营养不良且OTX2基因有新突变患者的临床特征，并将这些特征与先前报道的病例进行比较。
我们采用直接测序法，对142例患有莱伯先天性黑矇（LCA）或早发性视网膜营养不良（EORD）的患者进行OTX2基因突变筛查。所有患者均接受了包括视网膜电图和视网膜成像在内的详细眼科检查。
仅鉴定出一个OTX2基因突变。在一名患有婴儿期起病视网膜营养不良的7岁男性中鉴定出一种新的杂合p.S138X终止突变。该突变在其父母及181份献血者样本中均未出现。患者有婴儿期生长发育迟缓、喂养困难及生长激素缺乏的病史。从1岁起就出现视力差和夜盲。眼底检查发现视乳头周围有色素沉着环，整个眼底视网膜色素上皮有细微颗粒状色素沉着。暗适应闪光视网膜电图a波异常且波形呈电阴性，这与光感受器水平和光转导后功能障碍一致。迄今为止，视觉功能一直稳定。
已有报道称OTX2基因突变与眼部主要发育畸形、LCA等视网膜营养不良以及某些情况下的垂体功能障碍和癫痫发作有关。该病例进一步支持了OTX2在视网膜发育和垂体功能中的作用，并突出了与OTX2基因突变相关的一种新的视网膜营养不良表型。
