Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease.
Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease.
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DOI：
10.1016/j.kint.2020.02.022
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发表时间：
2020-08
影响因子：
19.6
通讯作者：
Cornec-Le Gall, Emilie
中科院分区：
文献类型：
--
作者：
Huynh, Vinh T.;Audrezet, Marie-Pierre;Sayer, John A.;Ong, Albert C.;Lefevre, Siriane;Le Brun, Valoris;Despres, Aurore;Senum, Sarah R.;Chebib, Fouad T.;Barroso-Gil, Miguel;Patel, Chirag;Mallett, Andrew J.;Goel, Himanshu;Mallawaarachchi, Amali C.;Van Eerde, Albertien M.;Ponlot, Eleonore;Kribs, Marc;Le Meur, Yannick;Harris, Peter C.;Cornec-Le Gall, Emilie
DNAJB11的单等位基因突变最近在七个家系中被描述为常染色体显性多囊肾病的非典型临床表现。DNAJB11编码内质网伴侣蛋白BiP的主要辅助因子之一，BiP是一种高效蛋白质折叠和运输所需的热休克蛋白。在这里，我们进行了一项国际合作研究，以更好地表征dnajb11相关表型。通过定向下一代测序、全外显子组测序或全基因组测序，在20个新的家系（54个受影响个体）中鉴定出13种不同的功能丧失变异。在目前报告的77例患者（27个家系）中，32例达到终末期肾病（范围55-89岁，中位年龄75岁）；男性和女性之间没有显著差异。虽然大多数患者表现为未增大的多囊肾，但在45岁以下患者中发现肾囊肿的情况并不一致。血管表型，包括颅内动脉瘤、胸主动脉扩张和颈动脉夹层存在于四个家系中。我们访问了Genomics England 100,000基因组计划数据，并在3934名患有各种肾脏和尿路疾病的先证者中发现了9名DNAJB11的致病性变异。8例先证者临床诊断为囊性肾病，1例先证者肾钙化症。没有发现其他可能解释肾脏疾病的致病变异。利用公开的GnomAD数据库，计算出DNAJB11的遗传患病率为0.85/ 10000人。因此，在非典型囊性或间质性肾脏疾病中建立精确的诊断是至关重要的，在随访、遗传咨询、预后评估、治疗管理和选择活体肾脏供体方面具有重要意义。
Monoallelic mutations of DNAJB11 were recently described in seven pedigrees with atypical clinical presentations of autosomal dominant polycystic kidney disease. DNAJB11 encodes one of the main cofactors of the endoplasmic reticulum chaperon BiP, a heat-shock protein required for efficient protein folding and trafficking. Here we conducted an international collaborative study to better characterize the DNAJB11-associated phenotype. Thirteen different loss-of-function variants were identified in 20 new pedigrees (54 affected individuals) by targeted next-generation sequencing, whole-exome sequencing or whole-genome sequencing. Amongst the 77 patients (27 pedigrees) now in total reported, 32 reached end stage kidney disease (range, 55–89 years, median age 75); without a significant difference between males and females. While a majority of patients presented with non-enlarged polycystic kidneys, renal cysts were inconsistently identified in patients under age 45. Vascular phenotypes, including intracranial aneurysms, dilatation of the thoracic aorta and dissection of a carotid artery were present in four pedigrees. We accessed Genomics England 100,000 genomes project data, and identified pathogenic variants of DNAJB11 in nine of 3934 probands with various kidney and urinary tract disorders. The clinical diagnosis was cystic kidney disease for eight probands and nephrocalcinosis for one proband. No additional pathogenic variants likely explaining the kidney disease were identified. Using the publicly available GnomAD database, DNAJB11 genetic prevalence was calculated at 0.85/10.000 individuals. Thus, establishing a precise diagnosis in atypical cystic or interstitial kidney disease is crucial, with important implications in terms of follow-up, genetic counseling, prognostic evaluation, therapeutic management, and for selection of living kidney donors.
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DOI：
10.1083/jcb.201709072
发表时间：
2018-01-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Klaips CL;Jayaraj GG;Hartl FU
通讯作者：
Hartl FU
影响因子：
15.9
作者：
Besse, Whitney;Dong, Ke;Somlo, Stefan
通讯作者：
Somlo, Stefan
DOI：
10.2215/cjn.01220211
发表时间：
2011-10-01
影响因子：
9.8
作者：
Bollee, Guillaume;Dahan, Karin;Knebelmann, Bertrand
通讯作者：
Knebelmann, Bertrand
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
64.8
作者：
Dickinson ME;Flenniken AM;Ji X;Teboul L;Wong MD;White JK;Meehan TF;Weninger WJ;Westerberg H;Adissu H;Baker CN;Bower L;Brown JM;Caddle LB;Chiani F;Clary D;Cleak J;Daly MJ;Denegre JM;Doe B;Dolan ME;Edie SM;Fuchs H;Gailus-Durner V;Galli A;Gambadoro A;Gallegos J;Guo S;Horner NR;Hsu CW;Johnson SJ;Kalaga S;Keith LC;Lanoue L;Lawson TN;Lek M;Mark M;Marschall S;Mason J;McElwee ML;Newbigging S;Nutter LM;Peterson KA;Ramirez-Solis R;Rowland DJ;Ryder E;Samocha KE;Seavitt JR;Selloum M;Szoke-Kovacs Z;Tamura M;Trainor AG;Tudose I;Wakana S;Warren J;Wendling O;West DB;Wong L;Yoshiki A;International Mouse Phenotyping Consortium;Jackson Laboratory;Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS);Charles River Laboratories;MRC Harwell;Toronto Centre for Phenogenomics;Wellcome Trust Sanger Institute;RIKEN BioResource Center;MacArthur DG;Tocchini-Valentini GP;Gao X;Flicek P;Bradley A;Skarnes WC;Justice MJ;Parkinson HE;Moore M;Wells S;Braun RE;Svenson KL;de Angelis MH;Herault Y;Mohun T;Mallon AM;Henkelman RM;Brown SD;Adams DJ;Lloyd KC;McKerlie C;Beaudet AL;Bućan M;Murray SA
通讯作者：
Murray SA