Dong Xiaoyun, Dong Huiru, Kang Wenqing, Xiong Hong, Xu Bangli, Lin Fatao, Zheng Xuan
Department of Neonatal Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450066, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Dec 10;38(12):1185-1189. doi: 10.3760/cma.j.cn511374-20200607-00416.
To explore the clinical characteristics, genetic basis and clinical treatment of seven neonates with congenital nephrogenic diabetes insipidus (NDI).
Clinical data of the patients were collected. High-throughput sequencing was carried out to detect potential variants. Sanger sequencing was used to verify the results.
The patients were all males, with the age of onset being 10 to 21 days. All patients were admitted to the hospital for intermittent fever as the first symptom during the neonatal period. Additional symptoms had included polydipsia and polyuria. After the treatment, 5 patients had recovered, the remainders still had NDI symptoms and developmental retardation. Five children were found 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, and two hemizygous deletions of the AVPR2/AQP2 gene. Among these, two were unreported previously. Cases 6 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.
AVPR2/AQP2 is the main pathogenic gene for congenital NDI, for which two novel pathogenic variants have been discovered in this study. Above results have provided a basis for clinical diagnosis and genetic counseling for the affected pedigrees.
探讨7例先天性肾性尿崩症（NDI）新生儿的临床特征、遗传基础及临床治疗。
收集患者的临床资料。进行高通量测序以检测潜在变异。采用Sanger测序验证结果。
患者均为男性，发病年龄为10至21天。所有患者在新生儿期均以间歇性发热为首发症状入院。其他症状包括多饮和多尿。治疗后，5例患者康复，其余患者仍有NDI症状和发育迟缓。发现5名儿童携带AVPR2/AQP2基因的致病变异，其中包括1个c.645_646insGCACCTACCCTGGGTATCGCC的框内突变、2个c.541C>T和c.419C>A的错义突变，以及2个AVPR2/AQP2基因的半合子缺失。其中，2个变异此前未被报道。病例6和病例7是一对双胞胎。二者均携带已知致病的AVPR2/AQP2基因c.538G>A的纯合错义变异。
AVPR2/AQP2是先天性NDI的主要致病基因，本研究发现了2个新的致病变异。上述结果为受影响家系的临床诊断和遗传咨询提供了依据。
