Exome sequencing of Saudi Arabian patients with ADPKD

Renal Failure

Jiankang Li¹  Kai Huang¹  Xiaoyan Huang¹  Lusheng Wang²  Fahad A. Al-Muhanna³  Tamer S. Ahmed Elsalamouni³  Mohammed Shakil Akhtar³  Afnan F. Almuhanna³  Feras Al-Kuwaiti³  Rudaynah A. Alali³  Shamim Shaikh Mohiuddin³  Cyril Cyrus³  Amein K. Al-Ali³  Abdullah M. Al-Rubaish³  Arafat Ahmad³  Abdullah Al Hwiesh³  Chittibabu Vatte³  Mohammad Ahmad Albezra⁴  Matthew B. Lanktree⁵  Brendan Keating⁶ 

[1] BGI-Shenzhen;City University of Hong Kong;Imam Abdulrahman Bin Faisal University;King Fahd Military Medical Complex;McMaster University;University of Pennsylvania School of Medicine;

关键词: adpkd;    pkd1;    saudi arabia;    cftr;    egf;    tsc2;   

DOI  :  10.1080/0886022X.2019.1655453

来源: DOAJ

【 摘 要 】

Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and enlargement and dysfunction of the kidneys. The Consortium of Radiologic Imaging Studies of the Polycystic Kidney Disease (CRISP) cohort revealed that 89.1% had either a PKD1 or PKD2 mutation. Of the CRISP patients with a genetic cause detected, mutations in PKD1 accounted for 85%, while mutations in the PKD2 accounted for the remaining 15%. Here, we report exome sequencing of 16 Saudi patients diagnosed with ADPKD and 16 ethnically matched controls. Methods: Exome sequencing was performed using combinatorial probe-anchor synthesis and improved DNA Nanoballs technology on BGISEQ-500 sequencers (BGI, China) using the BGI Exome V4 (59 Mb) Kit. Identified variants were validated with Sanger sequencing. Results: With the exception of GC-rich exon 1, we obtained excellent coverage of PKD1 (mean read depth = 88) including both duplicated and non-duplicated regions. Of nine patients with typical ADPKD presentations (bilateral symmetrical kidney involvement, positive family history, concordant imaging, and kidney function), four had protein truncating PKD1 mutations, one had a PKD1 missense mutation, and one had a PKD2 mutation. These variants have not been previously observed in the Saudi population. In seven clinically diagnosed ADPKD cases but with atypical features, no PKD1 or PKD2 mutations were identified, but rare predicted pathogenic heterozygous variants were found in cystogenic candidate genes including PKHD1, PKD1L3, EGF, CFTR, and TSC2. Conclusions: Mutations in PKD1 and PKD2 are the most common cause of ADPKD in Saudi patients with typical ADPKD. Abbreviations: ADPKD: Autosomal dominant polycystic kidney disease; CFTR: Cystic fibrosis transmembrane conductance regulator; EGF: Epidermal growth factor; MCIC: Mayo Clinic Imaging Classification; PKD: Polycystic kidney disease; TSC2: Tuberous sclerosis complex 2

【 授权许可】

Unknown