第七届北京罕见病学术大会暨2019京津冀罕见病学术大会征文（195）

中国医学科学院北京协和医院儿科

简珊 魏骐骄 刘雨桐 王薇 周煜 全美盈 何艳燕 宋红梅 魏珉

通讯作者:魏珉

【摘要】

目的 探讨由TTC21B基因突变致肾单位肾痨（NPHP）12型的临床及基因学特点。方法 分析1例NPHP 12型患者的临床表现、实验室检查和基因测序结果，并文献复习。结果 患者，女，3岁11月龄。临床主要表现为蛋白尿、水肿、肾功能损害、高血压伴心力衰竭，并有内脏反位、短指/趾。尿蛋白电泳示以肾小球性蛋白尿为主，尿β2微球蛋白、尿α1微球蛋白等肾小管指标均明显增高。3岁11个月时进展到终末期肾病。基因全外显子测序显示TTC21B基因c.1552T＞C（p.C518R）、c.752T＞G（p.M251R）复合杂合突变，Sanger测序验证2个突变分别来自父母。c.752T＞G为新发突变。检索到10篇共47例存在TTC21B基因突变的患者。18例有完整肾脏病理资料，均有NPHP相关肾小管损害表现，且17/18例同时存在肾小球硬化。TTC21B基因c.626C> T（p.P209L）纯合突变患者的临床表现相对较轻。

结论 TTC21B基因突变患者往往同时存在肾小球硬化和肾小管间质损害。TTC21B基因c.626C> T（p.P209L）纯合突变患者的临床表现相对较轻。

【关键词】肾单位肾痨；TTC21B基因；终末期肾病；儿童

Mutations in TTC21B cause nephronophthisis in one Chinese child and literature review

JIAN Shan，WEI Qi-Jiao， LIU Yu-Tong， WANG Wei， ZHOU Yu， QUAN Mei-Ying， HE Yan-Yan， SONG Hong-Mei， WEI Min.

Department of Pediatrics， Peking Union Medical College Hospital， Beijing 100730， China (Wei M， Email: pumch_wm@126.com)

【Abstract】

Objective  To summarize and review the clinical data of one Chinese pediatric case with  nephronophthisis caused by the TTC21B gene mutations.

Methods  The clinical data of one Chinese child with nephronophthisis were summarized，including clinical manifestations， laboratory findings and imaging data. Mutation analysis of the TTC21B gene was performed by whole exome sequencing.

Results The case was a 3 years and 11 months old girl. The main clinical manifestations were proteinuria， edema，  renal dysfunction， high blood pressure with heart failure， situs inversus， and short phalanges. Urine protein electrophoresis showed glomerular proteinuria mostly， and renal tubular indicators such as urinary β2 microglobulin and urinary α1 microglobulin were significantly increased. When she was 3 yars and 11 months old， she progressed to the stage of end-stage renal disease (ESRD). This case carried compound heterozygous mutations c.1552T＞C（p.C518R）and c.752T＞G（p.M251R）， and c.1552T＞C（p.C518R）was a de novo mutation. Family mutation analysis revealed that the above mutations were derived from their parents. A review of the literature found that a total of 10 articles， including 47 cases who had TTC21B gene mutations in the world. 18 patients had complete renal pathological data， and all of them had NPHP-related renal tubular lesions， and 17/18 cases had glomerular sclerosis. The clinical manifestations of c.626C> T(p.P209L) homozygous mutations were relatively milder.

Conclusion We identified one Chinese pediatric case with compound heterozygous TTC21B gene mutations that progressed to the stage of end-stage renal disease very early. Mutations in the TTC21B gene can cause not only tubule interstitial lesions but also glomerular lesions. The clinical manifestations of TTC21B gene c.626C> T(p.P209L) homozygous mutations were relatively milder.

Key words  Nephronophthisis；TTC21B gene；end-stage renal disease；child