Dong Yan, Sheng Haihui, Chen Xueru, Yin Jun, Su Qing
Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
BMC Genet. 2006 Nov 14;7:53. doi: 10.1186/1471-2156-7-53.
Congenital nephrogenic diabetes insipidus (NDI) is a rare X-linked inherited disorder characterized by the excretion of large volumes of diluted urine and caused by mutations in arginine vasopressin receptor 2 (AVPR2) gene. To investigate the mutation of AVPR2 gene in a Chinese family with congenital NDI, we screened AVPR2 gene in two NDI patients and eight family members by PCR amplification and direct sequencing.
Five specific fragments, covering entire coding sequence and their flanking intronic sequences of AVPR2 gene, were not observed in both patients, while those fragments were all detected in the control subjects. Several different fragments around the AVPR2 locus were amplified step by step. It was revealed that a genomic fragment of 5,995-bp, which contained the entire AVPR2 gene and the last exon (exon 22) of the C1 gene, was deleted and a 3-bp (GAG) was inserted. Examination of the other family members showed that the mothers and the grandmother were carriers for this deletion.
Our findings suggest that the two patients in a Chinese family suffering from congenital NDI had a 5,995-bp deletion and 3-bp (GAG) insertion at Xq28. The deletion contained the entire AVPR2 gene and exon 22 of the C1 gene.
先天性肾性尿崩症(NDI)是一种罕见的X连锁遗传性疾病,其特征是排出大量稀释尿液,由精氨酸加压素受体2(AVPR2)基因突变引起。为了研究一个先天性NDI中国家系中AVPR2基因的突变情况,我们通过PCR扩增和直接测序对两名NDI患者和八名家庭成员进行了AVPR2基因筛查。
在两名患者中均未观察到覆盖AVPR2基因整个编码序列及其侧翼内含子序列的五个特定片段,而在对照受试者中均检测到了这些片段。逐步扩增了AVPR2基因座周围的几个不同片段。结果显示,一个包含整个AVPR2基因和C1基因最后一个外显子(外显子22)的5995 bp基因组片段缺失,并插入了一个3 bp(GAG)。对其他家庭成员的检查表明,母亲和祖母是这种缺失的携带者。
我们的研究结果表明,一个患有先天性NDI的中国家系中的两名患者在Xq28处存在5995 bp的缺失和3 bp(GAG)的插入。该缺失包含整个AVPR2基因和C1基因的外显子22。