摘要目的:探讨1例进展性IgA肾病合并 COQ8B相关肾病患儿的遗传学病因。 方法:选取2021年3月2日于北京大学第一医院就诊的1例患儿为研究对象。回顾性分析患儿的临床资料，采集患儿及其父母和姐姐的外周血样，提取基因组DNA，对患儿进行全外显子组测序，对候选变异进行Sanger测序家系验证。本研究通过北京大学第一医院医学伦理委员会的审查(伦理号：2016[1029])。结果:患儿为7岁男童，因蛋白尿8个月(7岁8月龄)行肾穿刺病理检查，诊断为轻至中度系膜增生性IgA肾病(M1E1S1T1C1)，予激素、环磷酰胺、环孢素及血管紧张素转换酶抑制剂治疗后，尿蛋白部分缓解。病程3.9年(10岁11月龄)发现血肌酐从病初53.8 mol/L升至86.7 mol/L，大量蛋白尿，再次行肾穿刺病理检查示局灶增生性IgA肾病(M0E0S1T0C0)。基因检测结果显示患儿携带 COQ8B基因c.737G>A(p.Ser246Asn)纯合错义变异，其父母与姐姐均检测到相同的杂合变异。根据美国医学遗传学与基因组学学会相关指南，该变异判定为致病性(PS1＋PM2_Supporting＋PM3＋PP3＋PP4)。予以患儿大剂量辅酶Q10联合激素和/或吗替麦考酚酯治疗，病程7.3年(14岁4月龄)血肌酐升至286 mol/L，进展为慢性肾脏病G3b期。 结论:COQ8B基因c.737G>A(p.Ser246Asn)纯合变异可能为患儿肾功能下降的遗传学病因。当IgA肾病患儿临床表现不典型、疗效不佳甚至出现肾功能减退时，应考虑合并其他疾病的可能。

abstractsObjective:To explore the genetic etiology and clinical outcome of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy. Methods:A child who was admitted to Peking University First Hospital on March 2, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples from the child and his parents and sister. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing. This study was approved by Medical Ethics Committee of the Peking University First Hospital (Ethics No. 2016[1029]).Results:The child, a 7-year-old boy who had developed proteinuria 8 months before, was diagnosed with IgA nephropathy (M1E1S1T1C1). With steroid, cyclophosphamide, cyclosporine and angiotensin-converting enzyme inhibitor therapy, partial remission of proteinuria was achieved. However, his serum creatinine level had increased from 53.8 mol/L at the onset of disease to 86.7 mol/L after 3.9 years, along with massive proteinuria. Kidney biopsy still indicated IgA nephropathy (M0E0S1T0C0). The child was found to harbor a homozygous c. 737G>A (p.Ser246Asn) missense variant of the COQ8B gene, for which his parents and sister were heterozygous carriers. The variant was predicted to be pathogenic (PS1+ PM2_Supporting+ PM3+ PP3+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics. The child was treated with high-dose coenzyme Q10 in combination with steroid and/or mycophenolate mofetil, though his serum creatinine level still increased to 286 mol/L after 7.3 years, which conformed to a chronic kidney disorder with glomerular filtration rate category of G3b. Conclusion:The homozygous c.737G>A missense variants of the COQ8B gene probably underlay the progressive kidney dysfunction in this child. For children with IgA nephropathy presenting with atypical clinical manifestations, unsatisfactory therapeutic effect, and/or early onset of kidney function decline, coexistence of other diseases should be suspected.