American journal of kidney diseases : the official journal of the National Kidney Foundation · 2008
Presence of de novo mutations in autosomal dominant polycystic kidney disease patients without family history.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
BACKGROUND: 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.
STUDY DESIGN: 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.
OUTCOME: Presence or absence of PKD1 or PKD2 pathogenic sequence variants in parents of affected offspring.
MEASUREMENTS: 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.
RESULTS: 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.
LIMITATIONS: Size of patient group. No direct examination of RNA.
CONCLUSION: Causes other than de novo pathogenic sequence variants may explain the negative family history of ADPKD in certain families.
STUDY DESIGN: 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.
OUTCOME: Presence or absence of PKD1 or PKD2 pathogenic sequence variants in parents of affected offspring.
MEASUREMENTS: 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.
RESULTS: 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.
LIMITATIONS: Size of patient group. No direct examination of RNA.
CONCLUSION: Causes other than de novo pathogenic sequence variants may explain the negative family history of ADPKD in certain families.