Cheong Hae Il, Cho Su Jin, Zheng Shou Huan, Cho Hee Yeon, Ha Il Soo, Choi Yong
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
J Korean Med Sci. 2005 Dec;20(6):1076-8. doi: 10.3346/jkms.2005.20.6.1076.
Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. There are three inheritance patterns of CNDI: the X-linked recessive form associated with vasopressin V2 receptor gene mutations, and the autosomal recessive and dominant forms associated with aquaporin-2 gene (AQP2) mutations. The evaluation for polyuria and polydipsia in a one-month-old Korean girl revealed no response to vasopressin and confirmed the diagnosis of CNDI. Because the child was female without family history of CNDI, her disease was thought to be an autosomal recessive form. We analyzed the AQP2 gene and detected a compound heterozygous missense point mutation: 70Ala (GCC) to Asp (GAC) in exon 1 inherited from her father and 187Arg (CGC) to His (CAC) in exon 3 inherited from her mother. The first mutation is located within the first NPA motif of the AQP2 molecule and the second one right after the second NPA motif. This is the first report to characterize AQP2 mutations in Korean patients with autosomal recessive CNDI, and expands the spectrum of AQP2 mutations by reporting two novel mutation, 70Ala (GCC) to Asp (GAC) and 187Arg (CGC) to His (CAC).
先天性肾性尿崩症（CNDI）是一种罕见的遗传性疾病，其特征是肾脏对血管加压素的抗利尿作用不敏感。CNDI有三种遗传模式：与血管加压素V2受体基因突变相关的X连锁隐性形式，以及与水通道蛋白2基因（AQP2）突变相关的常染色体隐性和显性形式。对一名1个月大韩国女孩的多尿和烦渴评估显示其对血管加压素无反应，从而确诊为CNDI。由于该患儿为女性且无CNDI家族史，其疾病被认为是常染色体隐性形式。我们分析了AQP2基因，检测到一个复合杂合错义点突变：从父亲遗传而来的外显子1中70位丙氨酸（GCC）突变为天冬氨酸（GAC），从母亲遗传而来的外显子3中187位精氨酸（CGC）突变为组氨酸（CAC）。第一个突变位于AQP2分子的第一个NPA基序内，第二个突变位于第二个NPA基序之后。这是首次对韩国常染色体隐性CNDI患者的AQP2突变进行特征描述的报告，并通过报告两个新突变，即70位丙氨酸（GCC）突变为天冬氨酸（GAC）和187位精氨酸（CGC）突变为组氨酸（CAC），扩展了AQP2突变谱。
