Application of targeted panel sequencing and whole exome sequencing for 76 Chinese families with retinitis pigmentosa
Application of targeted panel sequencing and whole exome sequencing for 76 Chinese families with retinitis pigmentosa
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DOI：
10.1002/mgg3.1131
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发表时间：
2020-01-20
影响因子：
2
通讯作者：
Shen, Yin
中科院分区：
文献类型：
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作者：
Dan, Handong;Huang, Xin;Shen, Yin
本研究旨在鉴定76个中国无亲缘关系视网膜色素变性（RP）家族的基因变异和分子病因。方法选取76个经临床诊断为综合征型或非综合征型RP的家庭作为研究对象。先证者的基因组DNA样本通过靶向面板或全外显子组测序进行分析。利用生物信息学分析、Sanger测序和可用的家族成员分离来验证测序数据并确认致病基因的身份。结果纳入研究的参与者包括62个表现为非综合征性RP的家庭，13个表现为Usher综合征的家庭，1个表现为Bardet-Biedl综合征的家庭。我们发现43个家族（56.6%）在15个基因中存在致病变异，包括RHO、PRPF31、USH2A、CLRN1、BBS2、CYP4V2、EYS、RPE65、CNGA1、CNGB1、PDE6B、MERTK、RP1、RP2和RPGR；此外，在USH2A、EYS、CLRN1、CERKL、RP1、CRB1、SLC7A14等7个常染色体隐性RP基因中，有12个家族（15.8%）仅有1个杂合变异。其余21个家族（27.6%）未检测到任何变异。我们还鉴定了67个潜在的致病基因变异，其中24个是新的。结论本研究发现的基因变异扩大了RP基因的变异频率和变异谱；此外，这些变异的识别为未来RP的诊断和治疗提供了基础线索。
Background This study aimed to identify the gene variants and molecular etiologies in 76 unrelated Chinese families with retinitis pigmentosa (RP). Methods In total, 76 families with syndromic or nonsyndromic RP, diagnosed on the basis of clinical manifestations, were recruited for this study. Genomic DNA samples from probands were analyzed by targeted panels or whole exome sequencing. Bioinformatics analysis, Sanger sequencing, and available family member segregation were used to validate sequencing data and confirm the identities of disease-causing genes. Results The participants enrolled in the study included 62 families that exhibited nonsyndromic RP, 13 that exhibited Usher syndrome, and one that exhibited Bardet-Biedl syndrome. We found that 43 families (56.6%) had disease-causing variants in 15 genes, including RHO, PRPF31, USH2A, CLRN1, BBS2, CYP4V2, EYS, RPE65, CNGA1, CNGB1, PDE6B, MERTK, RP1, RP2, and RPGR; moreover, 12 families (15.8%) had only one heterozygous variant in seven autosomal recessive RP genes, including USH2A, EYS, CLRN1, CERKL, RP1, CRB1, and SLC7A14. We did not detect any variants in the remaining 21 families (27.6%). We also identified 67 potential pathogenic gene variants, of which 24 were novel. Conclusion The gene variants identified in this study expand the variant frequency and spectrum of RP genes; moreover, the identification of these variants supplies foundational clues for future RP diagnosis and therapy.