A novel MERTK mutation causing retinitis pigmentosa.
A novel MERTK mutation causing retinitis pigmentosa.
复制标题
DOI：
10.1007/s00417-017-3679-9
复制
发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Grassi MA
中科院分区：
文献类型：
--
作者：
Al-Khersan H;Shah KP;Jung SC;Rodriguez A;Madduri RK;Grassi MA
视网膜色素变性（RP）是一种遗传异质性遗传性视网膜营养不良。迄今为止，已经有超过80个基因与RP有关。然而，该疾病表现出显著的基因座和等位基因异质性，目前的测试平台无法完全捕获。本研究的目的是描述一名RP患者在初始基因检测后未进行分子诊断的潜在突变。对受影响的先证者进行全外显子组测序。候选基因突变的选择是基于对预期遗传模式和预测致病性的坚持。对患者未受影响的母亲、受影响的兄弟和未受影响的姐妹完成MERTK的桑格测序，以确定遗传分期。在先证者已知的RP相关基因中发现了8个序列变异。序列分析显示，先证者是一个复合杂合子，在MERTK中有两个独立的突变，一个新的无义突变（c.2179C>T）和一个先前报道的错义突变（c.2530C>T）。先证者受影响的兄弟也有这两种突变。在未受影响的家庭成员中证实了预测的相位。我们的研究确定了一个新的无义突变MERTK在家庭与RP和没有事先的分子诊断。本研究还证明了外显子组测序在标准基因检测不成功时确定孟德尔疾病遗传基础的临床价值。
Retinitis pigmentosa (RP) is a genetically heterogeneous inherited retinal dystrophy. To date, over 80 genes have been implicated in RP. However, the disease demonstrates significant locus and allelic heterogeneity not entirely captured by current testing platforms. The purpose of the present study was to characterize the underlying mutation in a patient with RP without a molecular diagnosis after initial genetic testing. Whole-exome sequencing of the affected proband was performed. Candidate gene mutations were selected based on adherence to expected genetic inheritance pattern and predicted pathogenicity. Sanger sequencing of MERTK was completed on the patient’s unaffected mother, affected brother, and unaffected sister to determine genetic phase. Eight sequence variants were identified in the proband in known RP-associated genes. Sequence analysis revealed that the proband was a compound heterozygote with two independent mutations in MERTK, a novel nonsense mutation (c.2179C>T) and a previously reported missense variant (c.2530C>T). The proband’s affected brother also had both mutations. Predicted phase was confirmed in unaffected family members. Our study identifies a novel nonsense mutation in MERTK in a family with RP and no prior molecular diagnosis. The present study also demonstrates the clinical value of exome sequencing in determining the genetic basis of Mendelian diseases when standard genetic testing is unsuccessful.
登录
查看更多内容
DOI：
10.1084/jem.20041447
发表时间：
2004-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nandrot EF;Kim Y;Brodie SE;Huang X;Sheppard D;Finnemann SC
通讯作者：
Finnemann SC
影响因子：
1.7
作者：
Carnevali, Paolo;Baccash, Jonathan;Drmanac, Radoje
通讯作者：
Drmanac, Radoje
影响因子：
4.4
作者：
Wang, Nana Hsiang-Hua;Chen, Shih-Jen;Chen, Yuan-Tsong
通讯作者：
Chen, Yuan-Tsong
影响因子：
1.8
作者：
Anasagasti, Ander;Irigoyen, Cristina;Ruiz-Ederra, Javier
通讯作者：
Ruiz-Ederra, Javier
影响因子：
4.8
作者：
Tsou, Wen-I;Nguyen, Khanh-Quynh N.;Kotenko, Sergei V.
通讯作者：
Kotenko, Sergei V.