Next-generation sequencing-based molecular diagnosis of a Chinese patient cohort with autosomal recessive retinitis pigmentosa.

TitleNext-generation sequencing-based molecular diagnosis of a Chinese patient cohort with autosomal recessive retinitis pigmentosa.
Publication TypeJournal Article
Year of Publication2013
AuthorsFu, Q, Wang, F, Wang, H, Xu, F, Zaneveld, JE, Ren, H, Keser, V, Lopez, I, Tuan, H-F, Salvo, JS, Wang, X, Zhao, L, Wang, K, Li, Y, Koenekoop, RK, Chen, R, Sui, R
JournalInvest Ophthalmol Vis Sci
Date Published2013 Jun 14
KeywordsAdolescent, Adult, Asian People, Child, China, Cohort Studies, Female, Genes, Recessive, Humans, Male, Middle Aged, Molecular Diagnostic Techniques, Mutation, Retinitis Pigmentosa, Sequence Analysis, DNA, Young Adult

PURPOSE: Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease; therefore, an accurate molecular diagnosis is essential for appropriate disease treatment and family planning. The prevalence of RP in China had been reported at 1 in 3800, resulting in an estimated total of 340,000 Chinese RP patients. However, genetic studies of Chinese RP patients have been very limited. To date, no comprehensive molecular diagnosis has been done for Chinese RP patients. With the emergence of next-generation sequencing (NGS), comprehensive molecular diagnosis of RP is now within reach. The purpose of this study was to perform the first NGS-based comprehensive molecular diagnosis for Chinese RP patients.METHODS: Thirty-one well-characterized autosomal recessive RP (arRP) families were recruited. For each family, the DNA sample from one affected member was sequenced using our custom capture panel, which includes 163 retinal disease genes. Variants were called, filtered, and annotated by our in-house automatic pipeline.RESULTS: Twelve arRP families were successfully molecular diagnosed, achieving a diagnostic rate of approximately 40%. Interestingly, approximately 63% of the pathogenic mutations we identified are novel, which is higher than that observed in a similar study on European descent (45%). Moreover, the clinical diagnoses of two families were refined based on the pathogenic mutations identified in the patients.CONCLUSIONS: We conclude that comprehensive molecular diagnosis can be vital for an accurate clinical diagnosis of RP. Applying this tool on patients from different ethnic groups is essential for enhancing our knowledge of the global spectrum of RP disease-causing mutations.

Alternate JournalInvest Ophthalmol Vis Sci
PubMed ID23661369
PubMed Central IDPMC3684217
Grant List / CAPMC / CIHR / Canada
R01EY018571 / EY / NEI NIH HHS / United States
R01 EY022356 / EY / NEI NIH HHS / United States
R01 EY018571 / EY / NEI NIH HHS / United States
T32 GM008307 / GM / NIGMS NIH HHS / United States
T32EY007102 / EY / NEI NIH HHS / United States
R01EY022356 / EY / NEI NIH HHS / United States
T32 EY007102 / EY / NEI NIH HHS / United States

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