Kunjing Gong1,2,3,4, Min Xia1,2,3,4, Yaqin Wang1,2,3,4, Na Wang1,2,3,4, Ying Liu1,2,3,4, Victor Wei Zhang5,6, Hong Cheng7, Yuqing Chen8,9,10,11. 1. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, 100034, China. 2. Institute of Nephrology, Peking University, Beijing, 100034, China. 3. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, 100034, China. 4. Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, 100034, China. 5. AmCare Genomics Laboratory, Guangzhou, China. 6. Baylor College of Medicine Department of Human and Molecular Genetics, Houston, USA. 7. Division of Nephrology, Beijing AnZhen Hospital, Capital Medical University, Beijing, 100029, China. 8. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, 100034, China. cyq@bjmu.edu.cn. 9. Institute of Nephrology, Peking University, Beijing, 100034, China. cyq@bjmu.edu.cn. 10. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, 100034, China. cyq@bjmu.edu.cn. 11. Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, 100034, China. cyq@bjmu.edu.cn.
Abstract
Genes of UMOD, HNF1B, MUC1, REN and SEC61A1 were reported to be associated with autosomal dominant tubulointerstitial kidney disease (ADTKD). 48 probands and their family members (N = 27) were enrolled in this genetic screening study. A combination of methods was employed for comprehensive molecular analysis of both copy number variations (CNVs) and single nucleotide variants (SNVs). 35 probands were followed for years. The phenotype-genotype and genotype-outcome correlation were inferred from these datasets. In this cohort, 18 probands were diagnosed with ADTKD, according to Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Moreover, 11 probands were diagnosed with ADTKD-UMOD, one with ADTKD-REN and one with ADTKD-HNF1B, based on molecularly confirmed pathogenic variants. The 11 UMOD variants were mainly located in codons 28 to 289 and half of the variants were found to change the cysteine amino acid. According to the follow-up data, suspected ADTKD individuals had a better prognosis compared to ADTKD individuals (p = 0.029). Individuals with a cysteine substitution in the UMOD gene appeared to have a better prognosis than individuals with other amino acid substitutions (p = 0.015).
Genes of pan class="Gene">UMOD, n>an class="Gene">HNF1B, MUC1, REN and SEC61A1 were reported to be associated with autosomal dominant tubulointerstitial kidney disease (ADTKD). 48 probands and their family members (N = 27) were enrolled in this genetic screening study. A combination of methods was employed for comprehensive molecular analysis of both copy number variations (CNVs) and single nucleotide variants (SNVs). 35 probands were followed for years. The phenotype-genotype and genotype-outcome correlation were inferred from these datasets. In this cohort, 18 probands were diagnosed with ADTKD, according to Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Moreover, 11 probands were diagnosed with ADTKD-UMOD, one with ADTKD-REN and one with ADTKD-HNF1B, based on molecularly confirmed pathogenic variants. The 11 UMOD variants were mainly located in codons 28 to 289 and half of the variants were found to change the cysteine amino acid. According to the follow-up data, suspected ADTKD individuals had a better prognosis compared to ADTKD individuals (p = 0.029). Individuals with a cysteine substitution in the UMOD gene appeared to have a better prognosis than individuals with other amino acid substitutions (p = 0.015).
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