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ホシノ ジユンイチ
Hoshino Jiyun'ichi
星野 純一 所属 医学部 医学科（東京女子医科大学病院） 職種 教授・基幹分野長 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読なし |
| 表題 | Genetic Analysis of Severe Polycystic Liver Disease in Japan |
| 掲載誌名 | 正式名：Kidney360 略 称：Kidney360 ISSNコード：26417650/26417650 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 5(8),pp.1106-1115 |
| 著者・共著者 | Mizuno Hiroki, Besse Whitney, Sekine Akinari, Long Kelly T, Kurihara Shigekazu, Oba Yuki, Yamanouchi Masayuki, Hasegawa Eiko, Suwabe Tatsuya, Sawa Naoki, Ubara Yoshifumi, Somlo Stefan, Hoshino Junichi |
| 担当区分 | 最終著者,責任著者 |
| 発行年月 | 2024/08/01 |
| 概要 | BACKGROUND:Polycystic liver disease (PLD) is present in most patients with autosomal dominant polycystic kidney disease (ADPKD). PLD can alternatively be found with few, if any, kidney cysts as a diagnosis of isolated polycystic liver disease (ADPLD). Several genes are identified as causative for this spectrum of phenotypes, however, the relative incidence of genetic etiologies amongst patients with severe PLD is unknown.METHODS:Patients with ADPKD or ADPLD having severe PLD defined as height-adjusted total liver volume (hTLV) over 1,800mL/m were recruited. Subsequent clinical care was followed. Genetic analysis was performed using whole exome sequencing.RESULT:We enrolled and sequenced 49 patients (38 females, 11 males). Pathogenic or suspected pathogenic variants in polycystic disease genes were found in 44 out of 49 patients (90%). The disease gene was PKD1 in 20/44 (45%), PKD2 in 15/44 (34%), PRKCSH in 5/44 (11%), GANAB in 2/44 (5%), SEC63 in 1/44 (2%), and ALG8 in 1/44 (2%). The median hTLV was no different between genetically-defined ADPKD and ADPLD groups (4431 (range 1817-9148) versus 3437 (range 1860-8211) mL, p=0.77), whereas height-adjusted kidney volume (hTKV) was larger as expected in ADPKD than ADPLD (607 (range 190-2842) versus 179 (range 138-234) mL/m, p<0.01). Of the clinically-defined ADPKD cases, 20/38 (53%) were PKD1, 15/38 (39%) were PKD2, and 3 (8%) remain genetically unsolved. Among patients with a pathogenic PKD1 or PKD2 variant, we found three cases with a liver-dominant ADPKD (severe PLD with hTKV <250mL/m).CONCLUSION:ADPLD-related genes represent 20% of severe PLD patients in our cohort. Of those enrolled with ADPKD, we observed a higher frequency of PKD2 carriers than in any previously reported ADPKD cohorts. While there was no significant difference in the hTLV between PKD1 versus PKD2 patients in this cohort, our data suggests that enrollment on the basis of severe PLD may enrich for PKD2 patients. |
| DOI | 10.34067/KID.0000000000000461 |
| PMID | 38689396 |