Multimodal imaging analysis of macular dystrophy in patient with maternally inherited diabetes and deafness (MIDD) with m.3243A>G mutation
Multimodal imaging analysis of macular dystrophy in patient with maternally inherited diabetes and deafness (MIDD) with m.3243A>G mutation
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m.3243A>G 突变母系遗传性糖尿病伴耳聋 (MIDD) 患者黄斑营养不良的多模态成像分析
DOI：
10.1080/13816810.2021.1881978
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发表时间：
2021
影响因子：
1.2
通讯作者：
Kameya Shuhei
中科院分区：
文献类型：
--
作者：
Oishi Noriko;Kubota Daiki;Nakamoto Kenji;Takeda Yukito;Hayashi Mika;Gocho Kiyoko;Yamaki Kunihiko;Igarashi Tsutomu;Takahashi Hiroshi;Kameya Shuhei
目的：母系遗传性糖尿病和耳聋（MIDD）是由线粒体DNA中的异质性m.3243A>G突变引起的。MIDD的主要眼部特征是黄斑营养不良。本研究的目的是通过多模式高分辨率成像analysis.Methods：一个详细的病史和眼科检查，一个39岁的MIDD患者的表型特征进行识别。多模式成像包括眼底照相、眼底自发荧光成像、荧光素血管造影、谱域光学相干断层扫描、OCT血管造影和自适应光学成像。结果：1例39岁女性，感音神经性耳聋，合并糖尿病，临床表现为黄斑中心凹周围萎缩性改变，疑有MIDD。PCR-invader和WES方法显示患者外周血中线粒体DNA存在m.3243A>G突变，分别占异质性的29%和16.7%。光感受器变性和脉络膜视网膜萎缩主要发生在中心凹周围。多焦ERG显示中心凹周围反应降低。Goldmann视野在右眼的中央盲点和左眼的扩大盲点中是显著的。中央等压线两侧收缩。AO高分辨率视网膜成像结果显示，视网膜中央凹的视锥细胞密度明显降低，而视网膜色素上皮和脉络膜无明显萎缩。结论：WES分析可用于mtDNA m.3243A>G突变的检测。多模态成像分析结果表明，在MIDD患者中，视网膜中央凹的光感受器的原发性功能障碍可能先于RPE的功能障碍。
Purpose: Maternally inherited diabetes and deafness (MIDD) is caused by a heteroplasmic m.3243A>G mutation in the mitochondrial DNA. The main ocular feature in MIDD is macular dystrophy. The purpose of this study was to identify the phenotypical characteristics of a patient with MIDD by multimodal high-resolution imaging analyses.Methods: A detailed history and ophthalmic examination were performed on a 39-year-old patient with MIDD. Multi-modal imaging included fundus photography, fundus autofluorescence imaging, fluorescein angiography, spectral-domain optical coherence tomography, OCT-angiography, and adaptive optics imaging. The PCR-invader and whole exome sequencing (WES) methods were performed on the DNA of the patient.Results: A 39-year-old woman with sensorineural hearing loss, diabetes mellitus presented with atrophic perifoveal changes and MIDD was suspected. The PCR-invader and WES methods showed that the patient had a m.3243A>G mutation in the mitochondrial DNA with 29% and 16.7% of the heteroplasmy in the peripheral blood, respectively. Morphological analyses revealed that the areas of photoreceptor degeneration and chorioretinal atrophy were present mainly in the perifoveal region. Multifocal ERGs showed that the perifoveal responses were reduced. Goldmann visual field was significant for a cecocentral scotoma in the right eye and an enlarged blind spot in the left eye. The central isopter was constricted bilaterally. The results of high-resolution retinal imaging by AO revealed that the densities of the cone photoreceptor were significantly reduced in the fovea where no obvious atrophy of the RPE and choroid was observed.Conclusions: Our findings indicate that WES analysis can be used to detect the m.3243A>G mutation in the mtDNA. The results of multimodal imaging analyses indicated that the primary dysfunction of the photoreceptors in the fovea might precede the dysfunction of the RPE in patient with MIDD.