Universität zu Köln

Yu, Chih-Chuan, Lee, An-Fu, Kohl, Stefen, Lin, Ming-Yen, Cheng, Siao Muk, Hung, Chi-Chih, Chang, Jer-Ming, Chiu, Yi-Wen, Hwang, Shang-Jyh, Otto, Edgar A., Hildebrandt, Friedhelm and Hwang, Daw-Yang (2022). PKD2 founder mutation is the most common mutation of polycystic kidney disease in Taiwan. npj Genom. Med., 7 (1). BERLIN: NATURE PORTFOLIO. ISSN 2056-7944

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Abstract

Autosomal Dominant polycystic kidney disease (ADPKD) is the most common inherited adult kidney disease. Although ADPKD is primarily caused by PKD1 and PKD2, the identification of several novel causative genes in recent years has revealed more complex genetic heterogeneity than previously thought. To study the disease-causing mutations of ADPKD, a total of 920 families were collected and their diagnoses were established via clinical and image studies by Taiwan PKD Consortium investigators. Amplicon-based library preparation with next-generation sequencing, variant calling, and bioinformatic analysis was used to identify disease-causing mutations in the cohort. Microsatellite analysis along with genotyping and haplotype analysis was performed in the PKD2 p.Arg803* family members. The age of mutation was calculated to estimate the time at which the mutation occurred or the founder arrived in Taiwan. Disease-causing mutations were identified in 634 families (68.9%) by detection of 364 PKD1, 239 PKD2, 18 PKHD1, 7 GANAB, and 6 ALG8 pathogenic variants. 162 families (17.6%) had likely causative but non-diagnostic variants of unknown significance (VUS). A single PKD2 p.Arg803* mutation was found in 17.8% (164/920) of the cohort in Taiwan. Microsatellite and array analysis showed that 80% of the PKD2 p.Arg803* families shared the same haplotype in a 250 kb region, indicating those families may originate from a common ancestor 300 years ago. Our findings provide a mutation landscape as well as evidence that a founder effect exists and has contributed to a major percentage of the ADPKD population in Taiwan.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Yu, Chih-Chuan UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, An-Fu UNSPECIFIED UNSPECIFIED UNSPECIFIED Kohl, Stefen UNSPECIFIED UNSPECIFIED UNSPECIFIED Lin, Ming-Yen UNSPECIFIED UNSPECIFIED UNSPECIFIED Cheng, Siao Muk UNSPECIFIED UNSPECIFIED UNSPECIFIED Hung, Chi-Chih UNSPECIFIED UNSPECIFIED UNSPECIFIED Chang, Jer-Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Chiu, Yi-Wen UNSPECIFIED UNSPECIFIED UNSPECIFIED Hwang, Shang-Jyh UNSPECIFIED UNSPECIFIED UNSPECIFIED Otto, Edgar A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hildebrandt, Friedhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Hwang, Daw-Yang UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-684835
DOI:	10.1038/s41525-022-00309-w
Journal or Publication Title:	npj Genom. Med.
Volume:	7
Number:	1
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2056-7944
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOTYPE-PHENOTYPE CORRELATIONS; AUTOSOMAL-DOMINANT; LINKAGE DISEQUILIBRIUM; SEQUENCE VARIANTS; GENE-MUTATIONS; ENCODES; REGION Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68483