中华眼底病杂志

中华眼底病杂志

Sorsby眼底营养不良一家系

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目的观察Sorsby眼底营养不良(SFD)一家系的临床表现与基因突变位点。 方法 一个三代SFD家系4例患者及6名正常家系成员纳入研究。4例患者中,男女性各2例。所有受试者均行最佳矫正视力、非接触眼压计、裂隙灯显微镜、间接检眼镜、眼底彩色照相及频域光相干断层扫描检查。观察患者的眼底异常表现。采集所有受试者外周静脉血2 ml,提取全基因组DNA。运用二代测序法对先证者进行眼科疾病相关外显子捕获检测。运用Sanger测序法针对发现的致病位点对其他9位受试者进行分离验证。 结果 4例患者均在40~47岁出现明显视力下降。其中,2例男性患者为双眼发病,2例女性为单眼出现症状。4例患者均可见典型的黄斑区脉络膜新生血管(CNV)、后极部斑点状类玻璃膜疣沉积或局部外层视网膜萎缩等表现。基因检测结果显示,先证者的TIMP3基因第5号外显子上存在c.610A>T碱基杂合突变,导致该基因编码的第204位密码子由丝氨酸变为半胱氨酸(TIMP3:NM_000362:Exon5:c.A610T/p.S204C)。Sanger测序法验证结果显示,其他3例患者及第三代中的两名受试者在该位点均检测到与先证者相同的变异。 结论 该SFD家系患者均在40岁以后发病,以中心视力明显下降为主要特征;眼底可见典型的黄斑区CNV、后极部斑点状类玻璃膜疣沉积或局部外层视网膜萎缩等表现。TIMP3基因突变位点c.610A>T(p.S204C)是该家系的致病基因。

ObjectiveTo observe the clinical manifestation and gene mutation of a pedigree with Sorsby fundus dystrophy (SFD). Methods Ten members in 3 generations of a pedigree with SFD were included in this study. Four patients were observed in the pedigree, including 2 females and 2 males. All 10 members underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus color photography and spectral domain optical coherence tomography. Genomic DNA was extracted from peripheral venous blood which was collected from all the members. Relevant exons of ocular diseases were detected by the next generation sequencing method from the proband. The other members underwent Sanger verification. Results Among the four patients, fading eyesight was appeared at their 44, 46, 47 and 40 year-old respectively. The two male patients had bilateral morbidity, and the two female patients had monocular symptoms. DNA sequencing results showed that the proband, other 3 patients and 2 members from the Ⅲ generation had heterozygous mutation of TIMP3 gene in exon 5. The amino acid encoded by TIMP3 gene No.204 codon changed from serine to cysteine (TIMP3:NM_000362:Exon5:c.A610T/p.S204C). CoclusionsThe invasion time of all the patients in this pedigree is after their 40 year-old. Heterozygous mutation at c.610A>T (p.S204C) in TIMP3 gene is the causative gene of SFD in this pedigree.

关键词: 视网膜营养不良; TIMP3基因; 突变; 杂合子

Key words: Retinal dystrophies; TIMP3 gene; Mutation; Heterozygote

引用本文: 尹小芳, 叶祖科, 汤秀容, 梁影影, 黎彦豪, 罗书科, 卢彦. Sorsby眼底营养不良一家系. 中华眼底病杂志, 2018, 34(6): 546-551. doi: 10.3760/cma.j.issn.1005-1015.2018.06.005 复制

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