Genetic diagnosis and prenatal diagnosis of autosomal dominant polycystic kidney disease.
10.3760/cma.j.issn.1003-9406.2019.05.002
- Author:
Biyuan QIU
1
,
2
;
Jiyun YANG
3
,
4
,
5
Author Information
1. Medical Technology College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China
2. Department of Laboratory Medicine, Zigong Women's and Children's Hospital, Zigong, Sichuan 643000, China.
3. Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China
4. School of Medicine, University of Electronic Science and Technology, Chengdu, Sichuan 610054, China
5. Prenatal Diagnosis Center, Hospital of the University of Electronic Science and Technology, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China. Email: yangjiyun@yeah.net.
- Publication Type:Journal Article
- MeSH:
DNA Mutational Analysis;
Female;
Humans;
Mutation;
Pedigree;
Polycystic Kidney, Autosomal Dominant;
Pregnancy;
Prenatal Diagnosis;
TRPP Cation Channels
- From:
Chinese Journal of Medical Genetics
2019;36(5):419-423
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic etiology for 17 pedigrees affected with autosomal dominant polycystic kidney disease (ADPKD).
METHODS:Peripheral blood samples were derived from the probands and their parents with informed consent. Following DNA extraction, targeted capture and next generation sequencing were carried out in search for potential disease-causing variants. Sanger sequencing was used to validate candidate pathogenic variants co-segregating with the disease in each pedigree. Prenatal diagnosis was provided for one family.
RESULTS:Among the 17 probands, 14 PKD1 mutations and 3 PKD2 mutations were detected, which included 6 missense mutations, 4 nonsense mutations and 7 frameshift mutations. Of these, 8 have been associated with ADPKD previously and 9 were novel, which included c.7625G>T (p.Gly2542Val), c.3673C>T (p.Gln1225*), c.11048dupT (p.Thr3684Aspfs*38), c.9083_9084delAG (p.Glu3028Glyfs*40), c.10560delG (p.Pro3521Hisfs*6), c.7952_7974del TGTCCCTGAGGGTCCACACTGTG (p.Val2651Glyfs*2) of PKD1, and c.662T>G (p.Leu221*), c.1202_1203 insCT (p.Glu401Aspfs*2), and c.919 delA (p.Ser307Valfs*10) of PKD2. Prenatal testing showed that the fetus did not carry the same mutation as the proband.
CONCLUSION:Identification of causative mutations in the 17 pedigrees affected with ADPKD has provided a basis for genetic counseling and reproductive guidance. The novel findings have enriched the mutational spectrum of the PKD1 and PKD2 genes.
