Akiko Maeda1,2,3, Akiko Yoshida4,5, Kanako Kawai4, Yuki Arai4, Ryutaro Akiba4, Akira Inaba4, Seiji Takagi5,6, Ryoji Fujiki7, Yasuhiko Hirami5,6, Yasuo Kurimoto5,6, Osamu Ohara7, Masayo Takahashi4,5,6. 1. Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3 Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. amaeda@cdb.riken.jp. 2. Division of Ophthalmology, Institute of Biomedical Research and Innovation Hospital, Kobe, Japan. amaeda@cdb.riken.jp. 3. Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, USA. amaeda@cdb.riken.jp. 4. Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3 Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. 5. Division of Ophthalmology, Institute of Biomedical Research and Innovation Hospital, Kobe, Japan. 6. Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan. 7. Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
Abstract
PURPOSE: Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. STUDY DESIGN: Evaluation of diagnostic technology, Prospective, Clinical and experimental study. METHODS: A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. RESULTS: NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). CONCLUSIONS: The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.
PURPOSE:Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. STUDY DESIGN: Evaluation of diagnostic technology, Prospective, Clinical and experimental study. METHODS: A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. RESULTS: NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). CONCLUSIONS: The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.
Entities:
Keywords:
Genetic diagnosis; Japanese population; Molecular diagnosis; Retinitis Pigmentosa (RP)
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