探讨SSBP1基因突变致常染色体显性遗传性视神经萎缩(ADOA)合并终末期肾病患儿的临床特点及预后。

选择2021年3月31日因慢性肾脏病(CKD)病因未明于西安市儿童医院就诊的1例患儿(患儿1)为研究对象。采用回顾性分析方法，收集患儿1的临床资料，并获取全外显子组测序(WES)及Sanger测序验证结果。依据美国医学遗传学与基因组学学会(ACMG)制定的《遗传变异分类标准与指南》(以下简称为"ACMG指南")，对检测到的基因变异位点进行致病性评级。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》的要求。监护人对患儿1诊治过程均知情同意，并签署临床研究知情同意书。

①患儿1为男性，6岁6个月，以"发现身材矮小1^＋年，肾功能异常1个月"为主诉，2021年3月31日于西安市儿童医院肾脏科就诊。患儿1入院后实验室检查：肾功能检查结果显示，尿素氮浓度为15.26 mmol/L，肌酐为172 μmol/L，肾小球滤过率(GFR)为31.05 mL/(min·1.73 m²)，伴轻度代谢性酸中毒及轻度贫血；头颅MRI提示双侧小脑萎缩，双侧视力均为0.06。患儿1的WES结果显示，SSBP1基因存在c.320G>A(p.Arg107Gln)杂合变异，经Sanger测序验证来源于其父亲。对患儿1随访至10岁3个月时，GFR降至13.89 mL/(min·1.73 m²)，并进行腹膜透析治疗。②文献复习共纳入14例SSBP1基因突变致ADOA合并肾功能损害患者中，男性为10例，女性为4例，均于婴幼儿期及儿童期起病，但是诊断年龄均滞后；除肾功能损害外，其他系统受损最常见为感音神经性耳聋及神经系统表现。其基因突变中，以C.320G>A杂合错义突变常见(8/14)。

对于儿童期出现视神经萎缩者，若伴听力、神经系统及肾功能损害，尤其伴有家族史时，必要时行基因检查以明确诊断。

To investigate clinical characteristics and prognosis of children with autosomal dominant optic atrophy (ADOA) complicated with end-stage renal disease caused by SSBP1 gene mutation.

On March 31, 2021, a pediatric patient (Patient 1) with chronic kidney disease of unknown etiology who was treated at Xi′an Children′s Hospital was selected in this study. A retrospective analysis was performed to collect the clinical data of Patient 1, and whole-exome sequencing (WES) together with Sanger sequencing validation results were obtained. The pathogenicity of the detected variants was evaluated in accordance with the guidelines established by the American College of Medical Genetics and Genomics (ACMG). This study adhered to the requirements of the revised 2013 Declaration of Helsinki of the World Medical Association. Informed consent was obtained from the guardians of Patient 1.

① Patient 1 was a 6-year-6-month-old male who presented with a 1-year history of short stature and a 1-month history of abnormal renal function. He was admitted to the Department of Nephrology at Xi′an Children′s Hospital on March 31, 2021. Upon admission, auxiliary examinations revealed a blood urea level of 15.26 mmol/L, a serum creatinine level of 172 μmol/L, and an estimated glomerular filtration rate (GFR) of 31.05 mL/(min·1.73 m²), accompanied by mild metabolic acidosis and mild anemia. Cranial MRI indicated bilateral cerebellar atrophy, and visual acuity in both eyes was 0.06. Whole-exome sequencing (WES) identified a heterozygous c. 320G>A (p.Arg107Gln) variant in the SSBP1 gene, which was confirmed by Sanger sequencing to be of paternal origin. During follow-up, the GFR of patient 1 declined to 13.89 mL/(min·1.73 m²) by the age of 10 years and 3 months, at which point peritoneal dialysis was initiated. ② A literature review identified 14 reported patients with ADOA caused by SSBP1 gene variants and accompanied by renal impairment, including 10 males and 4 females. All patients had disease onset during infancy or childhood; however, diagnosis was delayed in all cases. Apart from renal involvement, the most common additional manifestations were sensorineural hearing loss and neurological symptoms. Among the identified variants, the heterozygous missense mutation c. 320G>A was the most frequent (8/14).

For pediatric patients presenting with optic atrophy accompanied by hearing loss, neurological involvement, and renal impairment-particularly when there is a positive family history-genetic testing should be performed when necessary to confirm the diagnosis.