Abstract：
Renal coloboma syndrome (RCS) and dominant optic atrophy are mainly caused by heterozygous mutations in PAX2 and OPA1, respectively. We describe a patient with digenic mutations in PAX2 and OPA1. A female infant was born without perinatal abnormalities. Magnetic resonance imaging at 4 months of age showed bilateral microphthalmia and optic nerve hypoplasia. Appropriate body size was present at 2 years of age, and mental development was favorable. Color fundus photography revealed severe retinal atrophy in both eyes. Electroretinography showed slight responses in the right eye, but no responses in the left eye, suggesting a high risk of blindness. Urinalysis results were normal, creatinine-based estimated glomerular filtration rate was 63.5 mL/min/1.73 m2, and ultrasonography showed bilateral hypoplastic kidneys. Whole exome sequencing revealed de novo frameshift mutations in PAX2 and OPA1. Both variants were classified as pathogenic (PVS1, PS2, PM2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Genetic testing for ocular diseases should be considered for patients with suspected RCS and a high risk of total blindness.
摘要：
肾缺损综合征（RCS）和显性视神经萎缩主要由PAX2和OPA1的杂合突变引起。我们描述了在PAX2和OPA1中具有双基因突变的患者。一名女婴出生时没有围产期异常。4月龄磁共振成像显示双侧小眼症和视神经发育不全。2岁时有适当的体型，智力发展是有利的。彩色眼底照相显示双眼严重视网膜萎缩。视网膜电描记术显示右眼有轻微反应,但是左眼没有反应，表明失明的风险很高。尿液分析结果正常,基于肌酐的估计肾小球滤过率为63.5mL/min/1.73m2,超声检查显示双侧肾脏发育不良.全外显子组测序显示PAX2和OPA1中从头移码突变。根据美国医学遗传学和基因组学学院（ACMG）的指南，两种变体均被分类为致病性（PVS1，PS2，PM2）。对于疑似RCS和完全失明高风险的患者，应考虑进行眼部疾病的基因检测。
