Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte
Abstract Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated t...
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Format: | Article |
Language: | English |
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BMC
2019-05-01
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Series: | Orphanet Journal of Rare Diseases |
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Online Access: | http://link.springer.com/article/10.1186/s13023-019-1070-0 |
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English |
format |
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DOAJ |
author |
Hyoung Soo Choi Qute Choi Jung-Ah Kim Kyong Ok Im Si Nae Park Yoomi Park Hee Young Shin Hyoung Jin Kang Hoon Kook Seon Young Kim Soo-Jeong Kim Inho Kim Ji Yoon Kim Hawk Kim Kyung Duk Park Kyung Bae Park Meerim Park Sang Kyu Park Eun Sil Park Jeong-A Park Jun Eun Park Ji Kyoung Park Hee Jo Baek Jeong Ho Seo Ye Jee Shim Hyo Seop Ahn Keon Hee Yoo Hoi Soo Yoon Young-Woong Won Kun Soo Lee Kwang Chul Lee Mee Jeong Lee Sun Ah. Lee Jun Ah Lee Jae Min Lee Jae Hee Lee Ji Won Lee Young Tak Lim Hyun Joo Jung Hee Won Chueh Eun Jin Choi Hye Lim Jung Ju Han Kim Dong Soon Lee The Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology |
spellingShingle |
Hyoung Soo Choi Qute Choi Jung-Ah Kim Kyong Ok Im Si Nae Park Yoomi Park Hee Young Shin Hyoung Jin Kang Hoon Kook Seon Young Kim Soo-Jeong Kim Inho Kim Ji Yoon Kim Hawk Kim Kyung Duk Park Kyung Bae Park Meerim Park Sang Kyu Park Eun Sil Park Jeong-A Park Jun Eun Park Ji Kyoung Park Hee Jo Baek Jeong Ho Seo Ye Jee Shim Hyo Seop Ahn Keon Hee Yoo Hoi Soo Yoon Young-Woong Won Kun Soo Lee Kwang Chul Lee Mee Jeong Lee Sun Ah. Lee Jun Ah Lee Jae Min Lee Jae Hee Lee Ji Won Lee Young Tak Lim Hyun Joo Jung Hee Won Chueh Eun Jin Choi Hye Lim Jung Ju Han Kim Dong Soon Lee The Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte Orphanet Journal of Rare Diseases Hereditary spherocytosis RBC membrane disorder Molecular diagnosis |
author_facet |
Hyoung Soo Choi Qute Choi Jung-Ah Kim Kyong Ok Im Si Nae Park Yoomi Park Hee Young Shin Hyoung Jin Kang Hoon Kook Seon Young Kim Soo-Jeong Kim Inho Kim Ji Yoon Kim Hawk Kim Kyung Duk Park Kyung Bae Park Meerim Park Sang Kyu Park Eun Sil Park Jeong-A Park Jun Eun Park Ji Kyoung Park Hee Jo Baek Jeong Ho Seo Ye Jee Shim Hyo Seop Ahn Keon Hee Yoo Hoi Soo Yoon Young-Woong Won Kun Soo Lee Kwang Chul Lee Mee Jeong Lee Sun Ah. Lee Jun Ah Lee Jae Min Lee Jae Hee Lee Ji Won Lee Young Tak Lim Hyun Joo Jung Hee Won Chueh Eun Jin Choi Hye Lim Jung Ju Han Kim Dong Soon Lee The Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology |
author_sort |
Hyoung Soo Choi |
title |
Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte |
title_short |
Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte |
title_full |
Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte |
title_fullStr |
Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte |
title_full_unstemmed |
Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte |
title_sort |
molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in korea: matching with osmotic fragility test and presence of spherocyte |
publisher |
BMC |
series |
Orphanet Journal of Rare Diseases |
issn |
1750-1172 |
publishDate |
2019-05-01 |
description |
Abstract Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS. |
topic |
Hereditary spherocytosis RBC membrane disorder Molecular diagnosis |
url |
http://link.springer.com/article/10.1186/s13023-019-1070-0 |
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doaj-abee68d56a8e4cec884160b107e54fd92020-11-25T03:21:21ZengBMCOrphanet Journal of Rare Diseases1750-11722019-05-0114111310.1186/s13023-019-1070-0Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyteHyoung Soo Choi0Qute Choi1Jung-Ah Kim2Kyong Ok Im3Si Nae Park4Yoomi Park5Hee Young Shin6Hyoung Jin Kang7Hoon Kook8Seon Young Kim9Soo-Jeong Kim10Inho Kim11Ji Yoon Kim12Hawk Kim13Kyung Duk Park14Kyung Bae Park15Meerim Park16Sang Kyu Park17Eun Sil Park18Jeong-A Park19Jun Eun Park20Ji Kyoung Park21Hee Jo Baek22Jeong Ho Seo23Ye Jee Shim24Hyo Seop Ahn25Keon Hee Yoo26Hoi Soo Yoon27Young-Woong Won28Kun Soo Lee29Kwang Chul Lee30Mee Jeong Lee31Sun Ah. Lee32Jun Ah Lee33Jae Min Lee34Jae Hee Lee35Ji Won Lee36Young Tak Lim37Hyun Joo Jung38Hee Won Chueh39Eun Jin Choi40Hye Lim Jung41Ju Han Kim42Dong Soon Lee43The Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology44Department of Pediatrics, Seoul National University Bundang HospitalDepartment of Laboratory Medicine, Chungnam National University HospitalDepartment of Laboratory Medicine, Seoul National University College of MedicineCancer Research Institute, Seoul National University College of MedicineCancer Research Institute, Seoul National University College of MedicineDivision of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of MedicineCancer Research Institute, Seoul National University College of MedicineCancer Research Institute, Seoul National University College of MedicineDepartment of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical SchoolDepartment of Laboratory Medicine, Chungnam National University School of MedicineDivision of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance HospitalDepartment of Internal Medicine, Seoul National University College MedicineDepartment of Pediatrics, Kyungpook National University School of MedicineDepartment of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of MedicineCancer Research Institute, Seoul National University College of MedicineDepartment of Pediatrics, Soonchunhyang University Hospital CheonanDepartment of Pediatrics, Chungbuk National University College of MedicineDepartment of Pediatrics, Ulsan University HospitalDepartment of Pediatrics, Gyeongsang National University College of MedicineDepartment of Pediatrics, Inje University College of MedicineDepartment of Pediatrics, Ajou University School of MedicineDepartment of pediatrics, Inje University College of Medicine, Busan Paik HospitalDepartment of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical SchoolDepartment of Pediatrics, Pusan National University College of MedicineDepartment of Pediatrics, Keimyung University School of Medicine and Dongsan Medical CenterDepartment of Pediatrics, Seoul National University College of MedicineDepartment of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical CenterDepartment of Pediatrics, Kyung Hee University School of MedicineDepartment of Internal Medicine, Hanyang University Guri HospitalDepartment of Pediatrics, Kyungpook National University School of MedicineDepartment of Pediatrics, Korea University College of MedicineDepartment of Pediatrics, University of Dankook College of MedicineDepartment of Internal Medicine, Daegu Fatima HospitalDepartment of Pediatrics, Korea Cancer Center HospitalDepartment of Pediatrics, College of Medicine, Yeungnam UniversityDepartment of Pediatrics, Chosun University School of MedicineDepartment of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical CenterDepartment of Pediatrics, Pusan National University College of MedicineDepartment of Pediatrics, Ajou University School of MedicineDepartment of Pediatrics, Dong-A University College of MedicineDepartment of Pediatrics, Daegu Catholic UniversityDepartment of Pediatrics, Sungkyunkwan University School of MedicineDivision of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of MedicineDepartment of Laboratory Medicine, Seoul National University College of MedicineThe Korean Society of HematologyAbstract Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.http://link.springer.com/article/10.1186/s13023-019-1070-0Hereditary spherocytosisRBC membrane disorderMolecular diagnosis |