Bichet D G, Birnbaumer M, Lonergan M, Arthus M F, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S
Département de Médecine, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Québec, Canada.
Am J Hum Genet. 1994 Aug;55(2):278-86.
X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine-vaso-pressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. We analyzed 31 independent NDI families to determine the nature and recurrence of AVPR2 mutations. Twenty-one new putative disease-causing mutations were identified: 113delCT, 253del35, 255de19, 274insG, V88M, R106C, 402delCT, C112R, Y124X, S126F, W164S, S167L, 684delTA, 804insG, W284X, A285P, W293X, R337X, and three large deletions or gene rearrangements. Five other mutations--R113W, Y128S, R137H, R181C, and R202C--that previously had been reported in other families were detected. There was evidence for recurrent mutation for four mutations (R113W, R137H, S167L, and R337X). Eight de novo mutation events were detected (274insG, R106C, Y128S, 167L [twice], R202C, 684delTA, and R337X). The origins were maternal (one), grandmaternal (one), and grandpaternal (six). In the 31 NDI families and 6 families previously reported by us, there is evidence both for mutation hot spots for nucleotide substitutions and for small deletions and insertions. More than half (58%) of the nucleotide substitutions in 26 families could be a consequence of 5-methyl-cytosine deamination at a CpG dinucleotide. Most of the small deletions and insertions could be attributed to slipped mispairing during DNA replication.
X连锁肾性尿崩症（NDI）是一种罕见疾病，由于位于Xq28的精氨酸血管加压素V2受体（AVPR2）基因突变，导致肾脏和肾外的AVPR2反应存在缺陷。我们分析了31个独立的NDI家系，以确定AVPR2突变的性质和复发情况。共鉴定出21个新的可能致病突变：113delCT、253del35、255de19、274insG、V88M、R106C、402delCT、C112R、Y124X、S126F、W164S、S167L、684delTA、804insG、W284X、A285P、W293X、R337X，以及三个大片段缺失或基因重排。还检测到另外五个先前在其他家系中报道过的突变——R113W、Y128S、R137H、R181C和R202C。有证据表明四个突变（R113W、R137H、S167L和R337X）存在复发突变。检测到8个新发突变事件（274insG、R106C、Y128S、167L[两次]、R202C、684delTA和R337X）。其起源分别为母亲（1例）、外祖母（1例）和祖父（6例）。在我们之前报道的31个NDI家系和6个家系中，有证据表明核苷酸替换以及小片段缺失和插入均存在突变热点。26个家系中超过一半（58%）的核苷酸替换可能是由于CpG二核苷酸处的5-甲基胞嘧啶脱氨基所致。大多数小片段缺失和插入可能归因于DNA复制过程中的错配滑动。
