Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History
Introduction: Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with polycystic kidneys who have a positive family history, >90% have pathogenic variants in PKD1 or PKD2, whereas only...
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Elsevier
2024-09-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924017972 |
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| author | Takuya Fujimaru Takayasu Mori Akinari Sekine Motoko Chiga Shintaro Mandai Hiroaki Kikuchi Yutaro Mori Yu Hara Tamami Fujiki Fumiaki Ando Koichiro Susa Soichiro Iimori Shotaro Naito Ryoichi Hanazawa Akihiro Hirakawa Toshio Mochizuki Tatsuya Suwabe Yoshifumi Ubara Shinichi Uchida Eisei Sohara |
| author_facet | Takuya Fujimaru Takayasu Mori Akinari Sekine Motoko Chiga Shintaro Mandai Hiroaki Kikuchi Yutaro Mori Yu Hara Tamami Fujiki Fumiaki Ando Koichiro Susa Soichiro Iimori Shotaro Naito Ryoichi Hanazawa Akihiro Hirakawa Toshio Mochizuki Tatsuya Suwabe Yoshifumi Ubara Shinichi Uchida Eisei Sohara |
| author_sort | Takuya Fujimaru |
| collection | DOAJ |
| description | Introduction: Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with polycystic kidneys who have a positive family history, >90% have pathogenic variants in PKD1 or PKD2, whereas only 1% have IFT140. However, approximately 40% of patients with polycystic kidneys without a family history do not have any pathogenic variants in PKD1 and PKD2. Methods: We conducted a comprehensive genetic analysis of 157 adult patients with polycystic kidneys whose parents did not have evident polycystic kidneys. We sequenced up to 92 genes associated with inherited cystic kidney disease, including IFT140. Results: Of the 157 patients, 7 (4.5%) presented with monoallelic loss-of-function variants in the IFT140 gene, 51 (32.5%) with pathogenic variants in the PKD1 or PKD2 gene, and 7 (4.5%) with pathogenic variants in other genes related to inherited kidney cystic disease. The proportion of monoallelic loss-of-function IFT140 variants in this cohort was higher than that in previously reported cohorts with polycystic kidneys who had a positive family history. None of the patients with monoallelic loss-of-function IFT140 variants had polycystic liver disease (PLD). Furthermore, patients with IFT140 pathogenic variants had a significantly smaller kidney volume and a remarkably higher estimated glomerular filtration rate (eGFR) than those with PKD1 pathogenic variants (P = 0.01 and 0.03, respectively). Conclusion: Because the phenotype of polycystic kidneys caused by the IFT140 gene is mild, parental kidney disease may be overlooked. Therefore, patients without a positive family history are more likely to carry pathogenic variants in IFT140. |
| format | Article |
| id | doaj-art-47fb6c1d18ba4084a64ed2c3f4354d95 |
| institution | OA Journals |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-47fb6c1d18ba4084a64ed2c3f4354d952025-08-20T02:33:36ZengElsevierKidney International Reports2468-02492024-09-01992685269410.1016/j.ekir.2024.06.021Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family HistoryTakuya Fujimaru0Takayasu Mori1Akinari Sekine2Motoko Chiga3Shintaro Mandai4Hiroaki Kikuchi5Yutaro Mori6Yu Hara7Tamami Fujiki8Fumiaki Ando9Koichiro Susa10Soichiro Iimori11Shotaro Naito12Ryoichi Hanazawa13Akihiro Hirakawa14Toshio Mochizuki15Tatsuya Suwabe16Yoshifumi Ubara17Shinichi Uchida18Eisei Sohara19Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Department of Nephrology, St Luke’s International Hospital, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanNephrology Center, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, JapanClinical Laboratory, Tokyo Medical and Dental University Hospital, Tokyo JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanPKD Nephrology Clinic, Tokyo, JapanNephrology Center, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, JapanNephrology Center, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Correspondence: Eisei Sohara, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.Introduction: Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with polycystic kidneys who have a positive family history, >90% have pathogenic variants in PKD1 or PKD2, whereas only 1% have IFT140. However, approximately 40% of patients with polycystic kidneys without a family history do not have any pathogenic variants in PKD1 and PKD2. Methods: We conducted a comprehensive genetic analysis of 157 adult patients with polycystic kidneys whose parents did not have evident polycystic kidneys. We sequenced up to 92 genes associated with inherited cystic kidney disease, including IFT140. Results: Of the 157 patients, 7 (4.5%) presented with monoallelic loss-of-function variants in the IFT140 gene, 51 (32.5%) with pathogenic variants in the PKD1 or PKD2 gene, and 7 (4.5%) with pathogenic variants in other genes related to inherited kidney cystic disease. The proportion of monoallelic loss-of-function IFT140 variants in this cohort was higher than that in previously reported cohorts with polycystic kidneys who had a positive family history. None of the patients with monoallelic loss-of-function IFT140 variants had polycystic liver disease (PLD). Furthermore, patients with IFT140 pathogenic variants had a significantly smaller kidney volume and a remarkably higher estimated glomerular filtration rate (eGFR) than those with PKD1 pathogenic variants (P = 0.01 and 0.03, respectively). Conclusion: Because the phenotype of polycystic kidneys caused by the IFT140 gene is mild, parental kidney disease may be overlooked. Therefore, patients without a positive family history are more likely to carry pathogenic variants in IFT140.http://www.sciencedirect.com/science/article/pii/S2468024924017972ADPKDIFT140inherited kidney cystic diseasenext-generation sequencingpolycystic kidney diseasetotal kidney volume |
| spellingShingle | Takuya Fujimaru Takayasu Mori Akinari Sekine Motoko Chiga Shintaro Mandai Hiroaki Kikuchi Yutaro Mori Yu Hara Tamami Fujiki Fumiaki Ando Koichiro Susa Soichiro Iimori Shotaro Naito Ryoichi Hanazawa Akihiro Hirakawa Toshio Mochizuki Tatsuya Suwabe Yoshifumi Ubara Shinichi Uchida Eisei Sohara Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History Kidney International Reports ADPKD IFT140 inherited kidney cystic disease next-generation sequencing polycystic kidney disease total kidney volume |
| title | Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History |
| title_full | Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History |
| title_fullStr | Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History |
| title_full_unstemmed | Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History |
| title_short | Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History |
| title_sort | importance of ift140 in patients with polycystic kidney disease without a family history |
| topic | ADPKD IFT140 inherited kidney cystic disease next-generation sequencing polycystic kidney disease total kidney volume |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924017972 |
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