Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis.
Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis.
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整个外显子组测序经常在早发性肾结石和早期肾钙质沉着症中检测到单基因原因。
DOI：
10.1016/j.kint.2017.06.025
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发表时间：
2018-01
影响因子：
19.6
通讯作者：
Hildebrandt F
中科院分区：
文献类型：
--
作者：
Daga A;Majmundar AJ;Braun DA;Gee HY;Lawson JA;Shril S;Jobst-Schwan T;Vivante A;Schapiro D;Tan W;Warejko JK;Widmeier E;Nelson CP;Fathy HM;Gucev Z;Soliman NA;Hashmi S;Halbritter J;Halty M;Kari JA;El-Desoky S;Ferguson MA;Somers MJG;Traum AZ;Stein DR;Daouk GH;Rodig NM;Katz A;Hanna C;Schwaderer AL;Sayer JA;Wassner AJ;Mane S;Lifton RP;Milosevic D;Tasic V;Baum MA;Hildebrandt F
肾结石的发病率持续上升。此前，我们通过对30个已知引起肾结石/肾钙症的基因进行基因小组测序，发现11.4%的成人发病的肾结石或肾钙质沉着症患者和16.7-20.8%的18岁前发病的患者可以检测到单基因病因。为了克服面板测序的局限性，我们在51个家庭中使用了完整的外显子组测序，这些家庭在25岁之前表现为至少有一个肾结石或有肾脏超声发现的肾钙质沉着症，以确定疾病的潜在分子遗传原因。在51个家系中的15个家系中，我们通过全外显子测序检测到一个单基因致病突变。共检测到7个隐性基因(AGXT、ATP6V1B1、CLDN16、CLDN19、GRHPR、SLC3A1、SLC12A1)突变，1个显性基因(SLC9A3R1)突变，1个基因(SLC34A1)突变。在19种不同的突变中，有7种以前没有被描述为致病。在一个家庭中，检测到117个基因中的一个可能代表导致肾结石的基因的表型突变。在15个家庭中的9个家庭中，基因诊断可能对结石的管理和预防具有特殊的意义。在我们的队列中，与较高的发现率相关的几个因素是肾结石/肾钙质沉着症的发病年龄较早，一个家庭中存在多个受影响的成员，以及存在血缘关系。因此，我们建立了完整的外显子组测序作为一种有效的分子遗传学诊断方法，用于对25岁前表现为肾结石/肾钙质沉着症的个体进行分子遗传学诊断。
The incidence of nephrolithiasis continues to rise. Previously, we showed that a monogenic cause could be detected in 11.4% of individuals with adult-onset nephrolithiasis or nephrocalcinosis and in 16.7-20.8% of individuals with onset before 18 years of age, using gene panel sequencing of 30 genes known to cause nephrolithiasis/nephrocalcinosis. To overcome the limitations of panel sequencing, we utilized whole exome sequencing in 51 families, who presented before age 25 years with at least one renal stone or with a renal ultrasound finding of nephrocalcinosis to identify the underlying molecular genetic cause of disease. In 15 of 51 families, we detected a monogenic causative mutation by whole exome sequencing. A mutation in seven recessive genes (AGXT, ATP6V1B1, CLDN16, CLDN19, GRHPR, SLC3A1, SLC12A1), in one dominant gene (SLC9A3R1), and in one gene (SLC34A1) with both recessive and dominant inheritance was detected. Seven of the 19 different mutations were not previously described as disease causing. In one family a causative mutation in one of 117 genes that may represent phenocopies of nephrolithiasis-causing genes was detected. In nine of 15 families the genetic diagnosis may have specific implications for stone management and prevention. Several factors that correlated with the higher detection rate in our cohort were younger age at onset of nephrolithiasis/nephrocalcinosis, presence of multiple affected members in a family, and presence of consanguinity. Thus, we established whole exome sequencing as an efficient approach towards a molecular genetic diagnosis in individuals with nephrolithiasis/nephrocalcinosis who manifest before age 25 years.
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影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
19.6
作者：
Lapointe, J. -Y.;Tessier, J.;Bonnardeaux, A.
通讯作者：
Bonnardeaux, A.
DOI：
10.2215/cjn.07540715
发表时间：
2016-04-01
影响因子：
9.8
作者：
Braun, Daniela Anne;Lawson, Jennifer Ashley;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm
影响因子：
19.6
作者：
Gee, Heon Yung;Otto, Edgar A.;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm
影响因子：
3.7
作者：
Lage MD;Pittman AM;Roncador A;Cellini B;Tucker CL
通讯作者：
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