Reed Berenice, McFann Kim, Kimberling William J, Pei York, Gabow Patricia A, Christopher Karen, Petersen Eric, Kelleher Catherine, Fain Pamela R, Johnson Ann, Schrier Robert W
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver and Health Sciences Center, Aurora, CO 80014, USA.
Am J Kidney Dis. 2008 Dec;52(6):1042-50. doi: 10.1053/j.ajkd.2008.05.015. Epub 2008 Jul 21.
At the University of Colorado Health Sciences Center, on detailed questioning, approximately 10% of patients with autosomal dominant polycystic kidney disease (ADPKD) gave no family history of ADPKD. There are several explanations for this observation, including occurrence of a de novo pathogenic sequence variant or extreme phenotypic variability. To confirm de novo sequence variants, we have undertaken clinical and genetic screening of affected offspring and their parents.
Case series.
SETTING & PARTICIPANTS: 24 patients with a well-documented ADPKD phenotype and no family history of polycystic kidney disease (PKD) and both parents of each patient.
Presence or absence of PKD1 or PKD2 pathogenic sequence variants in parents of affected offspring.
Abdominal ultrasound of affected offspring and their parents for ADPKD diagnosis. Parentage testing by genotyping. Complete screening of PKD1 and PKD2 genes by using genomic DNA from affected offspring; analysis of genomic DNA from both parents to confirm the absence or presence of all DNA variants found.
A positive diagnosis of ADPKD by means of ultrasound or genetic screening was made in 1 parent of 4 patients (17%). No PKD1 or PKD2 pathogenic sequence variants were identified in 10 patients (42%), whereas possible pathological DNA variants were identified in 4 patients (17%) and 1 of their respective parents. Parentage was confirmed in the remaining 6 patients (25%), and de novo sequence variants were documented.
Size of patient group. No direct examination of RNA.
Causes other than de novo pathogenic sequence variants may explain the negative family history of ADPKD in certain families.
在科罗拉多大学健康科学中心，经详细询问，约10%的常染色体显性多囊肾病（ADPKD）患者没有ADPKD家族史。对此现象有多种解释，包括出现新生致病序列变异或极端表型变异。为了确认新生序列变异，我们对受影响的后代及其父母进行了临床和基因筛查。
病例系列。
24例有充分记录的ADPKD表型且无多囊肾病（PKD）家族史的患者及其父母。
受影响后代的父母中是否存在PKD1或PKD2致病序列变异。
对受影响的后代及其父母进行腹部超声检查以诊断ADPKD。通过基因分型进行亲子鉴定。使用受影响后代的基因组DNA对PKD1和PKD2基因进行全面筛查；分析父母双方的基因组DNA以确认所发现的所有DNA变异的有无。
4例患者的1名父母（17%）经超声或基因筛查确诊为ADPKD。10例患者（42%）未发现PKD1或PKD2致病序列变异，而4例患者（17%）及其各自的1名父母中发现了可能的病理性DNA变异。其余6例患者（25%）亲子鉴定结果得到确认，并记录了新生序列变异。
患者群体规模。未对RNA进行直接检测。
除新生致病序列变异外的其他原因可能解释某些家族中ADPKD的阴性家族史。
