Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy
Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy
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DOI：
10.1186/1471-2350-15-11
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发表时间：
2014-01-20
影响因子：
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通讯作者：
Gorin, Michael B.
中科院分区：
文献类型：
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作者：
Ortube, Maria Carolina;Strom, Samuel P.;Gorin, Michael B.
背景：一个儿科患者表现为快速进行性视力丧失、夜盲症和视网膜营养不良。这是ABCA 4基因p.Arg602Trp突变纯合性的首次报道。该儿童成为法律盲期内2 years.Case介绍：一个八岁的西班牙裔女性提出了双边视力下降后，发热性胃肠道疾病恶心和呕吐。广泛的检查包括儿科感染性疾病和风湿病学会诊。双眼的初始视力远视力为20/60，近视力为20/30。在2年期间发生了快速进行性视力丧失，导致双眼远距离视力为20/200。眼底检查显示血管变细和视网膜下多个水泡样隆起。光学相干断层扫描显示病变远多于临床明显不同程度的海拔。自体荧光成像显示了显著的和广泛的地理区域萎缩。在临床检查中表现为玻璃疣样的沉积物是高荧光的，与指示RPE细胞功能障碍的含有A2 e（N-亚视黄基-N-视黄乙醇胺）的脂褐质沉积物一致。视网膜电图与视锥细胞营养不良一致，视杆细胞功能相对保留。血液分析和流变学评价未发现弥漫性感染后/炎症过程的证据。通过荧光素血管造影、光学相干断层扫描、自体荧光成像和眼底照相术记录了她视网膜下水泡样病变的独特和快速进展。家庭谱系史揭示了血缘关系，她的父母是表兄弟。全外显子组测序的DNA分析显示纯合性p.Arg602Trp在ABCA 4 gene.Conclusion：儿科患者提出了一个惊人的临床表现和戏剧性的进展速度，是临床上更具有感染性或炎症过程的特点。该病例扩大了归因于ABCA 4突变的表型的多样性范围，并进一步支持全外显子组测序作为一种强大的新工具的作用，可用于帮助临床医生为具有挑战性的病例建立诊断。
Background: A pediatric patient presented with rapidly progressive vision loss, nyctalopia and retinal dystrophy. This is the first report of homozygosity for the p.Arg602Trp mutation in the ABCA4 gene. The child became legally blind within a period of 2 years.Case presentation: An eight year-old Hispanic female presented with bilateral decreased vision following a febrile gastrointestinal illness with nausea and vomiting. Extensive workup involved pediatric infectious disease and rheumatology consultations.Initial visual acuity was 20/60 at distance and 20/30 at near in both eyes. Rapidly progressive vision loss occurred during a 2-year period resulting in visual acuities of 20/200 at distance in both eyes. Fundus exam disclosed attenuated vessels and multiple subretinal blister-like elevations. Optical coherence tomography showed far more lesions than were clinically evident with different levels of elevation. Autofluorescence imagery showed dramatic and widespread geographic areas of atrophy. The deposits that appeared drusen-like on clinical exam were hyperfluorescent, consistent with lipofuscin deposits containing A2e (N-retinylidene-N-retinylethanolamine) indicative of RPE cell dysfunction. Electroretinography was consistent with cone dystrophy, with relative preservation of rod function. Blood analysis and rheumatology evaluation found no evidence of a diffuse post-infectious/inflammatory process. The unique and rapid progression of her subretinal blister-like lesions was documented by fluorescein angiography, optical coherence tomography, autofluorescence imagery, and fundus photography. Family pedigree history disclosed consanguinity, her parents being first cousins. DNA analysis by whole exomic sequencing revealed homozygosity of p.Arg602Trp in the ABCA4 gene.Conclusion: The pediatric patient presented with a striking clinical appearance and dramatic rate of progression that was clinically more characteristic of an infectious or inflammatory process. This case expands the diverse range of phenotypes attributed to ABCA4 mutations and further supports the role of whole exome sequencing as a powerful new tool available to aid clinicians in establishing diagnosis for challenging cases.