Cone dystrophy or macular dystrophy associated with novel autosomal dominant GUCA1A mutations
Cone dystrophy or macular dystrophy associated with novel autosomal dominant GUCA1A mutations
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发表时间：
2017-04
期刊：
影响因子：
2.2
通讯作者：
G. Manes;Sonia Mamouni;E. Hérald;A. Richard;A. Sénéćhal;Karim Aouad;B. Bocquet;I. Meunier;C. Hamel
中科院分区：
文献类型：
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作者：
G. Manes;Sonia Mamouni;E. Hérald;A. Richard;A. Sénéćhal;Karim Aouad;B. Bocquet;I. Meunier;C. Hamel
目的鸟苷酸环化酶激活因子1A基因（GUCA 1A）的16个不同突变已被证实可引起常染色体显性视锥细胞营养不良（adCOD）、视锥-视杆细胞营养不良（adCORD）、黄斑营养不良（adMD）和视网膜色素变性（RP）。本研究的目的是报告两个新的突变和患者的临床特征。方法临床检查包括视力和视野检查、眼底检查、高分辨率光谱域光学相干断层扫描（OCT）、眼底自体荧光成像、全视野和多焦视网膜电图（ERG）记录。通过桑格测序在12个法国adCOD、adCORD和adMD家族中筛选GUCA 1A。结果发现两个新的GUCA 1A突变，一个为c.302_304delTAG（p.Val101del），另一个为c.444T>A（p.Asp148Glu）。p.Asp148Glu突变影响EF 4手的一个Ca 2+结合氨基酸，而p.Val101del突变导致位于EF 3手的位置100和102处的两个Ca 2+结合天冬氨酸残基之间的缬氨酸-101的框内缺失。两个家庭都抱怨视力下降随着年龄的增长而恶化。然而，p.Asp148Glu突变存在于一个涉及视锥功能异常和黄斑萎缩缺失的adCOD家族中，而p.Val101del突变出现在另一个没有泛发性视锥缺陷的adMD家族中。结论本研究中描述的两种新突变与不同的表型相关，MD为p.Val101del，COD为p.Asp148Glu，没有家族内表型异质性。
Purpose Sixteen different mutations in the guanylate cyclase activator 1A gene (GUCA1A), have been previously identified to cause autosomal dominant cone dystrophy (adCOD), cone–rod dystrophy (adCORD), macular dystrophy (adMD), and in an isolated patient, retinitis pigmentosa (RP). The purpose of this study is to report on two novel mutations and the patients’ clinical features. Methods Clinical investigations included visual acuity and visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and full-field and multifocal electroretinogram (ERG) recordings. GUCA1A was screened by Sanger sequencing in a cohort of 12 French families with adCOD, adCORD, and adMD. Results We found two novel GUCA1A mutations—one amino acid deletion, c.302_304delTAG (p.Val101del), and one missense mutation, c.444T>A (p.Asp148Glu)—each of which was found in one family. The p.Asp148Glu mutation affected one of the Ca2+-binding amino acids of the EF4 hand, while the p.Val101del mutation resulted in the in-frame deletion of Valine-101, localized between two Ca2+-binding aspartic acid residues at positions 100 and 102 of the EF3 hand. Both families complained of visual acuity loss worsening with age. However, the p.Asp148Glu mutation was present in one family with adCOD involving abnormal cone function and an absence of macular atrophy, whereas p.Val101del mutation was encountered in another family with adMD without a generalized cone defect. Conclusions The two novel mutations described in this study are associated with distinct phenotypes, MD for p.Val101del and COD for p.Asp148Glu, with no intrafamilial phenotypic heterogeneity.