探讨少年型肾消耗病(NPHP)的表型特征及其分子致病机制。

选择2020年3月和8月，分别在西安市儿童医院被确诊为NPHP的2例患儿[患儿1(13岁女童)、患儿2(10岁男童)]为研究对象。采用回顾性分析法，对这2例患儿的NPHP表型、实验室检查结果进行分析，并应用全外显子组测序(WES)及Sanger测序与多重连接探针扩增(MLPA)技术，进行NPHP致病突变基因位点分析和家系验证。本研究遵循的程序符合西安市儿童医院伦理委员会规定，并通过该伦理委员会审查及批准(审批文号：伦20210023)，并且征得受试儿家属知情同意。

①2例患儿临床表现均为多饮、多尿、生长发育迟缓伴肾功能异常。②2个非血亲家系的2例患儿中，检测到相同的NPHP1基因"纯合"突变(c.1756C>T)，并且只在各自系谱的母亲NPHP1基因中检测到其中一个点突变。③对2例患儿及其各自父亲的NPHP1基因进行拷贝数变异(CNV)分析结果显示，2例患儿在2号染色体2q13存在覆盖NPHP1基因1~20号外显子的杂合缺失，均遗传自各自系谱父亲的NPHP1基因突变。

NPHP患儿的临床表现不典型，基因检测有助于明确NPHP患儿的复杂突变，为临床对该病患儿的诊断及预后判断提供分子致病依据，并为家系提供遗传咨询。

To explore phenotypic features and molecular pathogenic mechanism of juvenile nephronophthisis (NPHP).

Two children (case 1, 13-year-old girl; case 2, 10-year-old boy) diagnosed with NPHP in Xi′an Children′s Hospital in March and August, 2020, respectively were selected into this study. Clinical phenotypes and laboratory findings of 2 children with NPHP were retrospectively analyzed. Whole exome sequencing (WES), Sanger sequencing and multiplex ligationdependent probe amplification (MLPA) were carried out to detect potential variant and family verification.The procedure followed in this study was in accordance with the regulations of the Ethics Committee of Xi′an Children′s Hospital, and was reviewed and approved by the Ethics Committee (Approval No.20210023), and written informed consents were obtained from the families of the subject children.

①Two cases had polydipsia, polyuria, and growth retardation with abnormal kidney function. ②Identical " pure" mutations in the NPHP1 gene (c.1756C>T) were detected in 2 children from 2 non-blood-related families, and only one of the point mutations in the maternal NPHP1 gene was detected in the respective lineage. ③A complete heterozygous deletion of NPHP1 (exon 1-20) in the other allele was found in each of the two children by copy number variation (CNV) analysis, which was inherited from their father of each pedigree.

NPHP has an atypical clinical manifestations. Genetic testing is helpful in identifying complicated mutations in children with NPHP, which could provide a molecular basis for clinical diagnosis and prognosis, as well as genetic counseling for them.