Noninvasive genetic testing for type IV collagen nephropathy using oral mucosa DNA sampling in children with haematuria
Jiaojiao Liu,
Dayin Zhou,
Xiaowen Wang,
Tong Shen,
Chunyan Wang,
Rufeng Dai,
Xinli Han,
Lin Huang,
Wenli Xu,
Jing Chen,
Yihui Zhai,
Jia Rao,
Duan Ma,
Qian Shen,
Hong Xu
Affiliations
Jiaojiao Liu
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Dayin Zhou
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Xiaowen Wang
Department of Nephrology and Rheumatology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Tong Shen
Department of Pediatrics, Xiamen Maternal and Child Health Hospital, Xiamen, China
Chunyan Wang
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Rufeng Dai
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Xinli Han
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Lin Huang
Department of Nephrology and Rheumatology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Wenli Xu
Department of Pediatrics, Xiamen Maternal and Child Health Hospital, Xiamen, China
Jing Chen
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Yihui Zhai
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Jia Rao
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Duan Ma
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China
Qian Shen
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Hong Xu
Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China
Objective Hematuria is one of the most common conditions in children, and increase the risk of chronic kidney disease. Persistent hematuria may be the earliest manifestation of type IV collagen-related nephropathy. Early diagnosis is essential for optimized therapy. Due to the invasive nature of kidney biopsy and the high cost of whole exome sequencing, its application in the diagnosis of isolated hematuria is rare. Hence, we performed noninvasive and convenient genetic testing approaches for type IV collagen-related nephropathy.Methods We used noninvasive oral mucosa sampling as an alternative method for DNA isolation for genetic testing and designed a panel targeting three type IV collagen nephropathy-related genes in children with hematuria. Children with persistent hematuria unaccompanied by clinically significant proteinuria or renal insufficiency who underwent genetic testing using a hematuria panel were enrolled.Results Thirty-seven of 112 (33.0%) patients were found to have a genetic variant in COL4A3/A4/A5. Pathogenic/likely pathogenic COL4A3/A4/A5 variants were identified in 17 of the 112 patients analyzed (15.2%), which were considered to explain their hematuria manifestations. In addition, variants of unknown significance (VUSs) were found in 17.8% (20/112) of patients. Furthermore, we observed a much greater COL4A3/A4/A5 variant detection rate in patients with a positive family history or more severe hematuria (RBC ≥ 20/HP) or with coexisting microalbuminuria (59.2% vs. 12.7%, p < 0.001; 64.0% vs. 24.1%, p < 0.001; 66.7% vs. 30.1%, p = 0.025).Conclusions We present the high prevalence of variants in COL4A genes in a multicenter pediatric cohort with hematuria, which requires close monitoring and long-term follow-up.
