PDF(Pubmed)
Abstract：
OBJECTIVE: Bi-allelic variants in CABP4 are associated with congenital cone-rod synaptic disorder, which has also been classified, electrophysiologically, as incomplete congenital stationary night blindness (iCSNB). We describe clinical findings in a patient who demonstrated an unusual macular optical coherence tomography (OCT) phenotype, not previously reported in this condition.
METHODS: Our patient underwent multimodal retinal imaging, international standard full-field ERG testing and whole genome sequencing.
RESULTS: The patient was a 60-year-old woman with non-progressive visual impairment since birth, nystagmus and preference for dim lighting. Clinical fundus examination was unremarkable. OCT imaging revealed a hypo-reflective zone under an elevated fovea in both eyes. ERGs showed an electronegative DA10 response, with severely abnormal light-adapted responses. Whole genome sequencing revealed homozygosity for a known pathogenic variant in CABP4. No variants were found in other genes that could explain the patient\'s phenotype.
CONCLUSIONS: OCT findings of foveal elevation and an underlying hypo-reflective zone are novel in this condition. Whilst the clinical history was similar to achromatopsia and other cone dysfunction syndromes, ERG findings suggested disease associated with CACNA1F or CABP4. As CACNA1F is X-linked, CABP4 was more likely, and confirmed on genetic testing. The patient saw better in dim light, confirming that night blindness is not a feature of CABP4-associated disease. Our case highlights the value of ERGs in discriminating between causes of cone dysfunction, and extends the range of retinal imaging phenotypes reported in this disorder.
METHODS: Our patient underwent multimodal retinal imaging, international standard full-field ERG testing and whole genome sequencing.
RESULTS: The patient was a 60-year-old woman with non-progressive visual impairment since birth, nystagmus and preference for dim lighting. Clinical fundus examination was unremarkable. OCT imaging revealed a hypo-reflective zone under an elevated fovea in both eyes. ERGs showed an electronegative DA10 response, with severely abnormal light-adapted responses. Whole genome sequencing revealed homozygosity for a known pathogenic variant in CABP4. No variants were found in other genes that could explain the patient\'s phenotype.
CONCLUSIONS: OCT findings of foveal elevation and an underlying hypo-reflective zone are novel in this condition. Whilst the clinical history was similar to achromatopsia and other cone dysfunction syndromes, ERG findings suggested disease associated with CACNA1F or CABP4. As CACNA1F is X-linked, CABP4 was more likely, and confirmed on genetic testing. The patient saw better in dim light, confirming that night blindness is not a feature of CABP4-associated disease. Our case highlights the value of ERGs in discriminating between causes of cone dysfunction, and extends the range of retinal imaging phenotypes reported in this disorder.
摘要：
目的：CABP4的双等位基因变异与先天性锥杆突触障碍有关，也被分类了，电生理学，不完全先天性固定夜盲症（iCSNB）。我们描述了一名表现出异常黄斑光学相干断层扫描（OCT）表型的患者的临床发现，以前没有报告过这种情况。
方法：我们的患者接受了多模态视网膜成像，国际标准的全现场ERG测试和全基因组测序。
结果：患者是一名60岁女性，自出生以来患有非进行性视力障碍，眼球震颤和偏爱昏暗的灯光。临床眼底检查无异常。OCT成像显示，双眼中央凹下方有一个低反射区。ERG显示出电负性DA10反应，具有严重异常的光适应反应。全基因组测序揭示了CABP4中已知致病变体的纯合性。在其他基因中没有发现可以解释患者表型的变异。
结论：在这种情况下，中央凹抬高和潜在的低反射区的OCT发现是新颖的。虽然临床病史与色盲和其他视锥功能障碍综合征相似，ERG发现提示与CACNA1F或CABP4相关的疾病。由于CACNA1F是X连接的，CABP4更有可能，并在基因检测中证实。病人在昏暗的光线下看得更好，证实夜盲症不是CABP4相关疾病的特征。我们的案例强调了ERGs在区分锥体功能障碍的原因中的价值，并扩展了该疾病中报告的视网膜成像表型的范围。
方法：我们的患者接受了多模态视网膜成像，国际标准的全现场ERG测试和全基因组测序。
结果：患者是一名60岁女性，自出生以来患有非进行性视力障碍，眼球震颤和偏爱昏暗的灯光。临床眼底检查无异常。OCT成像显示，双眼中央凹下方有一个低反射区。ERG显示出电负性DA10反应，具有严重异常的光适应反应。全基因组测序揭示了CABP4中已知致病变体的纯合性。在其他基因中没有发现可以解释患者表型的变异。
结论：在这种情况下，中央凹抬高和潜在的低反射区的OCT发现是新颖的。虽然临床病史与色盲和其他视锥功能障碍综合征相似，ERG发现提示与CACNA1F或CABP4相关的疾病。由于CACNA1F是X连接的，CABP4更有可能，并在基因检测中证实。病人在昏暗的光线下看得更好，证实夜盲症不是CABP4相关疾病的特征。我们的案例强调了ERGs在区分锥体功能障碍的原因中的价值，并扩展了该疾病中报告的视网膜成像表型的范围。
