Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG)
The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology...
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MDPI AG
2021-05-01
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| author | Eu Jeen Yang Ye Jee Shim Heung Sik Kim Young Tak Lim Ho Joon Im Kyung-Nam Koh Hyery Kim Jin Kyung Suh Eun Sil Park Na Hee Lee Young Bae Choi Jeong Ok Hah Jae Min Lee Jung Woo Han Jae Hee Lee Young-Ho Lee Hye Lim Jung Jung-Sook Ha Chang-Seok Ki on behalf of the Benign Hematology Committee of the Korean Pediatric Hematology Oncology Group (KPHOG) |
| author_facet | Eu Jeen Yang Ye Jee Shim Heung Sik Kim Young Tak Lim Ho Joon Im Kyung-Nam Koh Hyery Kim Jin Kyung Suh Eun Sil Park Na Hee Lee Young Bae Choi Jeong Ok Hah Jae Min Lee Jung Woo Han Jae Hee Lee Young-Ho Lee Hye Lim Jung Jung-Sook Ha Chang-Seok Ki on behalf of the Benign Hematology Committee of the Korean Pediatric Hematology Oncology Group (KPHOG) |
| author_sort | Eu Jeen Yang |
| collection | DOAJ |
| description | The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of <i>ITGB3</i> was the most common, followed by c.2333A>C (p.Gln778Pro) of <i>ITGB2B</i>. Known variants of GT, including c.917A>C (p.His306Pro) of <i>ITGB3</i> and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of <i>ITGA2B</i>, were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of <i>ITGB3</i> and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of <i>ITGA2B</i>, were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel <i>RASGRP2</i> variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs. |
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| spelling | doaj.art-6fc2de33d0504ec28a1592a0ea0e89b52023-11-21T18:29:34ZengMDPI AGGenes2073-44252021-05-0112569310.3390/genes12050693Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG)Eu Jeen Yang0Ye Jee Shim1Heung Sik Kim2Young Tak Lim3Ho Joon Im4Kyung-Nam Koh5Hyery Kim6Jin Kyung Suh7Eun Sil Park8Na Hee Lee9Young Bae Choi10Jeong Ok Hah11Jae Min Lee12Jung Woo Han13Jae Hee Lee14Young-Ho Lee15Hye Lim Jung16Jung-Sook Ha17Chang-Seok Ki18on behalf of the Benign Hematology Committee of the Korean Pediatric Hematology Oncology Group (KPHOG)Department of Pediatrics, Pusan National University School of Medicine, Pusan National University Children’s Hospital, Yangsan 50612, KoreaDepartment of Pediatrics, Keimyung University School of Medicine, Keimyung University Dongsan Hospital, Daegu 42601, KoreaDepartment of Pediatrics, Keimyung University School of Medicine, Keimyung University Daegu Dongsan Hospital, Daegu 41931, KoreaDepartment of Pediatrics, Pusan National University School of Medicine, Pusan National University Children’s Hospital, Yangsan 50612, KoreaDepartment of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul 05505, KoreaDepartment of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul 05505, KoreaDepartment of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul 05505, KoreaDepartment of Pediatrics, Korea Cancer Center Hospital, Seoul 01812, KoreaDepartment of Pediatrics, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, Jinju 52727, KoreaDepartment of Pediatrics, Cha Bundang Medical Center, Cha University, Seongnam 13496, KoreaDepartment of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, Suwon 16499, KoreaDepartment of Pediatrics, Daegu Fatima Hospital, Daegu 41199, KoreaDepartment of Pediatrics, Yeungnam University College of Medicine, Daegu 42415, KoreaDepartment of Pediatrics, Yonsei University College of Medicine, Yonsei University Health System, Seoul 03722, KoreaDepartment of Pediatrics, Chungbuk National University School of Medicine, Chungbuk National University Hospital, Cheongju 28644, KoreaDepartment of Pediatrics, Hanyang University Seoul Hospital, Seoul 04763, KoreaDeparment of Pediatrics, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul 03181, KoreaDepartment of Laboratory Medicine, Keimyung University School of Medicine, Keimyung University Dongsan Hospital, Daegu 42601, KoreaGreen Cross Genome, Yongin 16924, KoreaThe diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of <i>ITGB3</i> was the most common, followed by c.2333A>C (p.Gln778Pro) of <i>ITGB2B</i>. Known variants of GT, including c.917A>C (p.His306Pro) of <i>ITGB3</i> and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of <i>ITGA2B</i>, were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of <i>ITGB3</i> and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of <i>ITGA2B</i>, were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel <i>RASGRP2</i> variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs.https://www.mdpi.com/2073-4425/12/5/693blood platelet disordershigh-throughput nucleotide sequencingthrombastheniawhole exome sequencingwhole genome sequencing |
| spellingShingle | Eu Jeen Yang Ye Jee Shim Heung Sik Kim Young Tak Lim Ho Joon Im Kyung-Nam Koh Hyery Kim Jin Kyung Suh Eun Sil Park Na Hee Lee Young Bae Choi Jeong Ok Hah Jae Min Lee Jung Woo Han Jae Hee Lee Young-Ho Lee Hye Lim Jung Jung-Sook Ha Chang-Seok Ki on behalf of the Benign Hematology Committee of the Korean Pediatric Hematology Oncology Group (KPHOG) Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG) Genes blood platelet disorders high-throughput nucleotide sequencing thrombasthenia whole exome sequencing whole genome sequencing |
| title | Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG) |
| title_full | Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG) |
| title_fullStr | Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG) |
| title_full_unstemmed | Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG) |
| title_short | Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG) |
| title_sort | genetic confirmation and identification of novel variants for glanzmann thrombasthenia and other inherited platelet function disorders a study by the korean pediatric hematology oncology group kphog |
| topic | blood platelet disorders high-throughput nucleotide sequencing thrombasthenia whole exome sequencing whole genome sequencing |
| url | https://www.mdpi.com/2073-4425/12/5/693 |
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