不同基因突变致肾单位肾痨及相关综合征患儿临床表型特点及基因分析

目的 提高对肾单位肾痨（nephronophthisis,NPHP）及相关综合征患儿临床表型和基因特点的认识。方法 回顾性分析2018年1月—2022年11月河北医科大学第二医院儿科诊治的8例NPHP及相关综合征患儿的临床资料，对其临床特征和基因检测结果进行分析。结果 8例NPHP患儿中，男5例，女3例，起病年龄15个月至12岁，就诊时均存在不同程度肾功能异常。8例患儿中，2例以发育落后首发，2例以贫血为首发，2例为体检发现肾功能异常；肾外表现包括心血管异常2例，骨骼发育异常2例，肝功能异常1例，视网膜色素变性1例，内脏镜面转位1例。8例患儿肾脏B超均有结构改变，4例尿常规显示存在轻至中度蛋白尿。5例为NPHP1基因突变，NPHP3、IFT140、TTC21B基因突变各1例，共发现4个新突变位点。结论 NPHP及相关综合征患儿常以发育落后或贫血为首发表现，部分患儿合并肾外表现。对不明原因肾功能异常患儿，应考虑到NPHP及相关综合征，高通量测序技术有助于明确诊断。中国当代儿科杂志，2023,25(8):831-836]

Clinical phenotype characteristics and genetic analysis in children with nephronophthisis and related syndromes caused by different gene mutations

Objective To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children.Methods A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed.Results Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered.Conclusions Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.