CEP78 is mutated in a distinct type of Usher syndrome.
CEP78 is mutated in a distinct type of Usher syndrome.
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CEP78 在一种独特类型的 Usher 综合征中发生突变
DOI：
10.1136/jmedgenet-2016-104166
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发表时间：
2017-03
影响因子：
4
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Fu Q;Xu M;Chen X;Sheng X;Yuan Z;Liu Y;Li H;Sun Z;Li H;Yang L;Wang K;Zhang F;Li Y;Zhao C;Sui R;Chen R
Usher综合征是一种以视觉损伤和听力损失为特征的遗传异质性疾病。尽管已经确定了与Usher综合征有关的十几个基因，但20-30%的患者的遗传基础仍然未知。在这项研究中，我们的目的是鉴定新的致病基因的一个独特亚型Usher综合征。对2个近亲家庭的Usher综合征患者进行眼科检查和听力测试。最初进行靶捕获测序是为了筛选已知视网膜致病位点的致病突变。应用全外显子组测序（WES）和全基因组测序（WGS）鉴定新型致病基因。采用RT-PCR和Sanger测序来评估鉴定的CEP78变异的剪接改变作用。来自两个独立家族的患者表现为轻度Usher综合征表型，以青少年或成人发病的锥杆营养不良和感音神经性听力损失为特征。WES和WGS发现了两个影响纤毛基因CEP78 mRNA剪接的纯合罕见变异。RT-PCR证实这两个变异体确实会导致剪接异常，导致蛋白翻译因移码而过早停止。我们的研究结果提供了证据，证明CEP78是Usher综合征的一个新的致病基因，表明纤毛病与光感受器细胞和内耳毛细胞中的Usher蛋白网络之间存在额外的联系。
Usher syndrome is a genetically heterogeneous disorder featured by combined visual impairment and hearing loss. Despite a dozen of genes involved in Usher syndrome having been identified, the genetic basis remains unknown in 20–30% of patients. In this study, we aimed to identify the novel disease-causing gene of a distinct subtype of Usher syndrome. Ophthalmic examinations and hearing tests were performed on patients with Usher syndrome in two consanguineous families. Target capture sequencing was initially performed to screen causative mutations in known retinal disease-causing loci. Whole exome sequencing (WES) and whole genome sequencing (WGS) were applied for identifying novel disease-causing genes. RT-PCR and Sanger sequencing were performed to evaluate the splicing-altering effect of identified CEP78 variants. Patients from the two independent families show a mild Usher syndrome phenotype featured by juvenile or adult-onset cone–rod dystrophy and sensorineural hearing loss. WES and WGS identified two homozygous rare variants that affect mRNA splicing of a ciliary gene CEP78. RT-PCR confirmed that the two variants indeed lead to abnormal splicing, resulting in premature stop of protein translation due to frameshift. Our results provide evidence that CEP78 is a novel disease-causing gene for Usher syndrome, demonstrating an additional link between ciliopathy and Usher protein network in photoreceptor cells and inner ear hair cells.
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DOI：
10.1126/science.1219240
发表时间：
2012-07-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
NHLBI Exome Sequencing Project
DOI：
10.1159/000016167
发表时间：
1998-01-01
期刊：
Community genetics
影响因子：
--
作者：
Espinos, C;Millan, J M;Najera, C
通讯作者：
Najera, C
DOI：
10.1161/circgenetics.108.829747
发表时间：
2009-02
期刊：
Circulation. Cardiovascular genetics
影响因子：
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作者：
Psaty BM;O'Donnell CJ;Gudnason V;Lunetta KL;Folsom AR;Rotter JI;Uitterlinden AG;Harris TB;Witteman JC;Boerwinkle E;CHARGE Consortium
通讯作者：
CHARGE Consortium
影响因子：
2.4
作者：
Sillibourne JE;Hurbain I;Grand-Perret T;Goud B;Tran P;Bornens M
通讯作者：
Bornens M
影响因子：
3.7
作者：
Bonnet C;Grati M;Marlin S;Levilliers J;Hardelin JP;Parodi M;Niasme-Grare M;Zelenika D;Délépine M;Feldmann D;Jonard L;El-Amraoui A;Weil D;Delobel B;Vincent C;Dollfus H;Eliot MM;David A;Calais C;Vigneron J;Montaut-Verient B;Bonneau D;Dubin J;Thauvin C;Duvillard A;Francannet C;Mom T;Lacombe D;Duriez F;Drouin-Garraud V;Thuillier-Obstoy MF;Sigaudy S;Frances AM;Collignon P;Challe G;Couderc R;Lathrop M;Sahel JA;Weissenbach J;Petit C;Denoyelle F
通讯作者：
Denoyelle F