七例新生儿期发病的先天性肾性尿崩症患儿的 临床及分子遗传学研究

Clinical characteristics and molecular genetics of seven neonates with congenital nephrogenic diabetes insipidus

目的 探讨新生儿期起病的先天性肾性尿崩症的临床特点、基因诊断及治疗。方法 收集7例新生儿期发病的先天性肾性尿崩症患儿的临床资料,应用高通量测序法筛查、Sanger测序法验证基因变异位点。结果 7例患儿均为男性,发病年龄在10~21天,均以间断发热为首发症状入院,有烦渴、多饮、多尿症状,经治疗5例症状缓解,2例仍有症状、发育落后。5例存在AVPR2基因变异,例1为c.645_646insGCACCTACCCTGGGTATCGCC整码变异;例2、4分别为c.541C>T、c.419C>A错义变异;例3、例5均为AVPR2基因半合子整体缺失。其中例1、4为未报道过的新变异。例6、例7患儿为双胎儿,均为AQP2基因第3外显子c.538G>A纯合错义突变所致,已有相关基因突变的报道。结论 AVPR2/AQP2基因为先天性肾性尿崩症的主要致病基因,新发现2种未见报道的变异位点,为先天性肾性尿崩症在新生儿期的临床诊断和遗传咨询提供了依据。

Objective To explore the clinical characteristics,genetic basis and clinical treatment ofseven neonates with congenital nephrogenic diabetes insipidus(NDI).Methods Clinical data of the patientswere collected.High-throughput sequencing was carried out to detect potential variants.Sanger sequencingwas used to verify the results,Results The patients were all males,with the age of onset being 10 to 21days.All patients were admitted to the hospital for intermittent fever as the first symptom during theneonatal period.Additional symptoms had included polydipsia and polyuria,After the treatment,5 patientshad recovered,the remainders still had NDl symptoms and developmental retardation.Five children werefound to harbor pathogenic variants of the AVPR2/AQP2 gene,which included one in-frame mutation of c.645_646insGCACCTACCCTGGGTATCGCC,two missense mutations of c.541C>T and c.419C>A,andtwo hemizygous deletions of the AVPR2/AQP2 gene.Among these,two were unreported previously.Cases6 and 7 were a pair of twins.Both had carried homozygous missense variants of c.538G>A of the AVPR2/AQP2 gene,which was known to be pathogenic,Conclusion AVPR2/AQP2 is the main pathogenic genefor congenital NDI,for which two novel pathogenic variants have been discovered in this study.Aboveresults have provided a basis for clinical diagnosis and genetic counseling for the affected pedigrees.