COQ2基因复合杂合突变致儿童孤立性肾病综合征1家系表型特征与预后分析

doi:10.12372/jcp.2026.25e1728

临床儿科杂志 ›› 2026, Vol. 44 ›› Issue (8): 733-738.doi: 10.12372/jcp.2026.25e1728

COQ2基因复合杂合突变致儿童孤立性肾病综合征1家系表型特征与预后分析

时嘉仪¹, 高春林¹, 贾丽丽¹, 陆云云¹, 孙涛¹, 朱小东², 夏正坤¹, 张沛¹()

¹ 南京医科大学金陵临床医学院儿科（江苏南京 210002）
² 南京大学医学院附属金陵医院国家肾脏病临床医学研究中心（江苏南京 210002）

收稿日期:2026-01-12 修回日期:2026-05-12 录用日期:2026-05-29 出版日期:2026-08-15 发布日期:2026-08-03
通讯作者: 张沛 E-mail:zhang.pei.2008@hotmail.com
作者简介:第一联系人：作者贡献（Authors’ Contributions）
时嘉仪负责论文构思，撰写论文；高春林、贾丽丽负责指导论文撰写；陆云云负责收集资料及病人随访；孙涛负责疾病诊疗；朱小东负责肾脏病理解释及诊断；夏正坤、张沛负责论文审核。
基金资助:
国家自然科学基金－面上项目(82570875);江苏省自然科学基金－面上项目(BK20242093)

Phenotypic characteristics and prognostic analysis of a pedigree with childhood isolated nephrotic syndrome caused by compound heterozygous mutations in the COQ2 gene

SHI Jiayi¹, GAO Chunlin¹, JIA Lili¹, LU Yunyun¹, SUN Tao¹, ZHU Xiaodong², XIA Zhengkun¹, ZHANG Pei¹()

¹ Jinling Clinical Medical College, Nanjing Medical University, Nanjing 210002, Jiangsu, China
² National Clinical Research Center of Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, Jiangsu, China

Received:2026-01-12 Revised:2026-05-12 Accepted:2026-05-29 Published:2026-08-15 Online:2026-08-03
Contact: ZHANG Pei E-mail:zhang.pei.2008@hotmail.com

摘要/Abstract

摘要：

本研究回顾性分析1个COQ2基因复合杂合突变所致儿童孤立性肾病综合征家系的临床资料，探讨其基因型与临床表型特征及预后相关性。该家系中两兄妹以肾病综合征起病，肾脏病理检查提示局灶节段性肾小球硬化；基因检测结果显示，两兄妹均携带COQ2基因c.233T>G（NM_001358921.2），p. (Met78Arg)及c.823A>G (NM_001358921.2)，p. (Thr275Ala)复合杂合突变，其中c.233T>G为新发变异。先证者（兄）初期基因检测未明确病因，给予激素及免疫抑制治疗无效，病情进行性加重最终死亡；其妹在发病后通过对先证者原始测序数据重分析早期明确诊断，及时给予大剂量辅酶Q₁₀替代治疗并减停激素，治疗1年后尿蛋白显著下降，临床症状及实验室指标明显改善，预后良好。本研究证实基因检测及数据定期重分析在该类遗传性肾脏病诊治中的重要价值，以及早期临床干预对改善患者预后的有效性，为原发性辅酶Q₁₀缺乏症相关肾病的诊断、治疗及遗传咨询提供了重要参考。

关键词: COQ2基因, 原发性辅酶Q₁₀缺乏症, 孤立性肾病综合征, 儿童

Abstract:

This study retrospectively analyzed clinical data from a family with childhood isolated nephrotic syndrome (INS) caused by compound heterozygous mutations in the COQ2 gene, to explore the correlations between genotype, clinical phenotypic characteristics, and prognosis. Two siblings in the family presented with INS, and renal pathological examination revealed focal segmental glomerulosclerosis (FSGS). Genetic testing identified that both siblings carried compound heterozygous mutations in COQ2: c.233T>G (NM_001358921.2), p.(Met78Arg) and c.823A>G (NM_001358921.2), p.(Thr275Ala), with c.233T>G being a de novo variant. The proband (elder brother) initially underwent genetic testing that failed to identify the etiology; treatment with glucocorticoids and immunosuppressants was ineffective, leading to progressive disease deterioration and eventual death. His younger sister, however, received an early diagnosis via reanalysis of the proband’s original sequencing data shortly after symptom onset. She was promptly administered high-dose coenzyme Q₁₀ replacement therapy and had glucocorticoids gradually tapered and discontinued. After one year of treatment, her urinary protein levels decreased significantly, and clinical symptoms and laboratory indicators improved markedly, with a favorable prognosis. This study confirms the critical value of genetic testing and periodic reanalysis of sequencing data in the diagnosis and management of such inherited kidney diseases, as well as the efficacy of early clinical intervention in improving patient outcomes. It provides important references for the diagnosis, treatment, and genetic counseling of primary coenzyme Q₁₀ deficiency-related nephropathy.

Key words: COQ2 gene, primary coenzyme Q₁₀ deficiency, isolated nephrotic syndrome, child

中图分类号:

时嘉仪, 高春林, 贾丽丽, 陆云云, 孙涛, 朱小东, 夏正坤, 张沛. COQ2基因复合杂合突变致儿童孤立性肾病综合征1家系表型特征与预后分析[J]. 临床儿科杂志, 2026, 44(8): 733-738.

SHI Jiayi, GAO Chunlin, JIA Lili, LU Yunyun, SUN Tao, ZHU Xiaodong, XIA Zhengkun, ZHANG Pei. Phenotypic characteristics and prognostic analysis of a pedigree with childhood isolated nephrotic syndrome caused by compound heterozygous mutations in the COQ2 gene[J]. Journal of Clinical Pediatrics, 2026, 44(8): 733-738.

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患儿	性别	起病年龄		病初表现	尿液检测	血生化	辅助检查
例1	男	1岁2个月		肾病综合征	尿蛋白++++；尿蛋白定量5.62 g/24 h	血白蛋白14.7 g·L^-1 血肌酐43.2 μmol·L^-1	双肾超声：双肾肾病样声像图胸部CT：双侧胸腹水
例2	女	11月龄		肾病综合征	尿蛋白++++；尿蛋白定量2.12 g/24 h	血白蛋白20.7 g·L^-1 血肌酐36.4 μmol·L^-1	双肾超声：未见异常胸部DR：双肺纹理稍增粗
患儿	肾脏病理		病理特征性表现			变异基因	突变位点	治疗	预后
例1	局灶节段性肾小球硬化		光镜：球形废弃（3/11），节段硬化（5/11）；电镜：足突广泛融合，大量畸形线粒体。			COQ2	c.233T>G c.823A>G	激素联合抗凝、利尿等对症支持治疗，间断予连续性肾脏替代治疗。	病情进行性加重，最终死亡
例2	局灶节段性肾小球硬化		光镜：节段硬化（6/35）；电镜：足突广泛融合，大量畸形线粒体。			COQ2	c.233T>G c.823A>G	激素联合抗凝、利尿等对症支持治疗，后改用辅酶Q₁₀ 100 mg 3次/d。	尿蛋白降至++，临床症状显著改善

COQ2基因复合杂合突变致儿童孤立性肾病综合征1家系表型特征与预后分析

Phenotypic characteristics and prognostic analysis of a pedigree with childhood isolated nephrotic syndrome caused by compound heterozygous mutations in the COQ2 gene

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