{"title":"家族性幼年高尿酸血症肾病:在一个 UMOD 基因末端总缺失的家族中重新审视 SLC8A1 基因","authors":"","doi":"10.1016/j.nefro.2023.09.007","DOIUrl":null,"url":null,"abstract":"<div><p>Autosomal dominant tubulointerstitial kidney disease (ADTKD) comprises a heterogeneous group of rare hereditary kidney diseases characterized by family history of progressive chronic kidney disease (CKD) with bland urine sediment, absence of significant proteinuria and normal or small-sized kidneys. Current diagnostic criteria require identification of a pathogenic variant in one of five genes – <em>UMOD</em>, <em>MUC1</em>, <em>REN</em>, <em>HNF1β</em>, <em>SEC61A1</em>. The most prevalent form of ADTKD is uromodulin-associated kidney disease (ADTKD-<em>UMOD</em>).</p><p>Genetic study of a Portuguese family diagnosed with familial juvenile hyperuricemic nephropathy (FJHN), one of the nosological entities in the spectrum of ADTKD, revealed a previously unreported large deletion in <em>UMOD</em> encompassing the entire terminal exon, which strictly cosegregated with CKD and hyperuricemia/gout, establishing the primary diagnosis of ADTKD-<em>UMOD</em>; as well as an ultra-rare nonsense <em>SLC8A1</em> variant cosegregating with the <em>UMOD</em> deletion in patients that consistently exhibited an earlier onset of clinical manifestations.</p><p>Since the terminal exon of <em>UMOD</em> does not encode for any of the critical structural domains or amino acid residues of mature uromodulin, the molecular mechanisms underlying the pathogenicity of its deletion are unclear and require further research.</p><p>The association of the <em>SLC8A1</em> locus with FJHN was first indicated by the results of a genome-wide linkage analysis in several multiplex families, but those data have not been subsequently confirmed. Our findings in this family revive that hypothesis.</p></div>","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"44 4","pages":"Pages 576-581"},"PeriodicalIF":2.0000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0211699523001480/pdfft?md5=d3a85b67fb355dbf72634ff71c1043ee&pid=1-s2.0-S0211699523001480-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Familial juvenile hyperuricemic nephropathy: Revisiting the SLC8A1 gene, in a family with a novel terminal gross deletion in the UMOD gene\",\"authors\":\"\",\"doi\":\"10.1016/j.nefro.2023.09.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Autosomal dominant tubulointerstitial kidney disease (ADTKD) comprises a heterogeneous group of rare hereditary kidney diseases characterized by family history of progressive chronic kidney disease (CKD) with bland urine sediment, absence of significant proteinuria and normal or small-sized kidneys. Current diagnostic criteria require identification of a pathogenic variant in one of five genes – <em>UMOD</em>, <em>MUC1</em>, <em>REN</em>, <em>HNF1β</em>, <em>SEC61A1</em>. The most prevalent form of ADTKD is uromodulin-associated kidney disease (ADTKD-<em>UMOD</em>).</p><p>Genetic study of a Portuguese family diagnosed with familial juvenile hyperuricemic nephropathy (FJHN), one of the nosological entities in the spectrum of ADTKD, revealed a previously unreported large deletion in <em>UMOD</em> encompassing the entire terminal exon, which strictly cosegregated with CKD and hyperuricemia/gout, establishing the primary diagnosis of ADTKD-<em>UMOD</em>; as well as an ultra-rare nonsense <em>SLC8A1</em> variant cosegregating with the <em>UMOD</em> deletion in patients that consistently exhibited an earlier onset of clinical manifestations.</p><p>Since the terminal exon of <em>UMOD</em> does not encode for any of the critical structural domains or amino acid residues of mature uromodulin, the molecular mechanisms underlying the pathogenicity of its deletion are unclear and require further research.</p><p>The association of the <em>SLC8A1</em> locus with FJHN was first indicated by the results of a genome-wide linkage analysis in several multiplex families, but those data have not been subsequently confirmed. Our findings in this family revive that hypothesis.</p></div>\",\"PeriodicalId\":18997,\"journal\":{\"name\":\"Nefrologia\",\"volume\":\"44 4\",\"pages\":\"Pages 576-581\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0211699523001480/pdfft?md5=d3a85b67fb355dbf72634ff71c1043ee&pid=1-s2.0-S0211699523001480-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nefrologia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0211699523001480\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nefrologia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0211699523001480","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Familial juvenile hyperuricemic nephropathy: Revisiting the SLC8A1 gene, in a family with a novel terminal gross deletion in the UMOD gene
Autosomal dominant tubulointerstitial kidney disease (ADTKD) comprises a heterogeneous group of rare hereditary kidney diseases characterized by family history of progressive chronic kidney disease (CKD) with bland urine sediment, absence of significant proteinuria and normal or small-sized kidneys. Current diagnostic criteria require identification of a pathogenic variant in one of five genes – UMOD, MUC1, REN, HNF1β, SEC61A1. The most prevalent form of ADTKD is uromodulin-associated kidney disease (ADTKD-UMOD).
Genetic study of a Portuguese family diagnosed with familial juvenile hyperuricemic nephropathy (FJHN), one of the nosological entities in the spectrum of ADTKD, revealed a previously unreported large deletion in UMOD encompassing the entire terminal exon, which strictly cosegregated with CKD and hyperuricemia/gout, establishing the primary diagnosis of ADTKD-UMOD; as well as an ultra-rare nonsense SLC8A1 variant cosegregating with the UMOD deletion in patients that consistently exhibited an earlier onset of clinical manifestations.
Since the terminal exon of UMOD does not encode for any of the critical structural domains or amino acid residues of mature uromodulin, the molecular mechanisms underlying the pathogenicity of its deletion are unclear and require further research.
The association of the SLC8A1 locus with FJHN was first indicated by the results of a genome-wide linkage analysis in several multiplex families, but those data have not been subsequently confirmed. Our findings in this family revive that hypothesis.
期刊介绍:
Nefrología is the official publication of the Spanish Society of Nephrology. The Journal publishes articles on basic or clinical research relating to nephrology, arterial hypertension, dialysis and kidney transplants. It is governed by the peer review system and all original papers are subject to internal assessment and external reviews. The journal accepts submissions of articles in English and in Spanish languages.