Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination
Background: Hereditary hemolytic anemia (HHA) is defined as a group of heterogeneous and rare diseases caused by defects of red blood cell (RBC) metabolism and RBC membrane, which leads to lysis or premature clearance. The aim of this study was to investigate individuals with HHA for potential disea...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/13/4/770 |
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| author | Namsu Kim Tae Yun Kim Ji Yoon Han Joonhong Park |
| author_facet | Namsu Kim Tae Yun Kim Ji Yoon Han Joonhong Park |
| author_sort | Namsu Kim |
| collection | DOAJ |
| description | Background: Hereditary hemolytic anemia (HHA) is defined as a group of heterogeneous and rare diseases caused by defects of red blood cell (RBC) metabolism and RBC membrane, which leads to lysis or premature clearance. The aim of this study was to investigate individuals with HHA for potential disease-causing variants in 33 genes reported to be associated with HHA. Methods: A total of 14 independent individuals or families diagnosed with suspected HHA, and in particular, RBC membranopathy, RBC enzymopathy, and hemoglobinopathy, were collected after routine peripheral blood smear testing. A custom designed panel, including the 33 genes, was performed using gene panel sequencing on the Ion Torrent PGM™ Dx System. The best candidate disease-causing variants were confirmed by Sanger sequencing. Results: Several variants of the HHA-associated genes were detected in 10 out of 14 suspected HHA individuals. After excluding those variants predicted to be benign, 10 pathogenic variants and 1 variant of uncertain significance (VUS) were confirmed in 10 individuals with suspected HHA. Of these variants, the p.Trp704Ter nonsense variant of <i>EPB41</i> and missense p.Gly151Asp variant of <i>SPTA1</i> were identified in two out of four hereditary elliptocytoses. The frameshift p.Leu884GlyfsTer27 variant of <i>ANK1</i>, nonsense p.Trp652Ter variant of the <i>SPTB</i>, and missense p.Arg490Trp variant of <i>PKLR</i> were detected in all four hereditary spherocytosis cases. Missense p.Glu27Lys, nonsense p.Lys18Ter variants, and splicing errors such as c.92 + 1G > T and c.315 + 1G > A within <i>HBB</i> were identified in four beta thalassemia cases. Conclusions: This study provides a snapshot of the genetic alterations in a cohort of Korean HHA individuals and demonstrates the clinical utility of using gene panels in HHA. Genetic results can provide precise clinical diagnosis and guidance regarding medical treatment and management for some individuals. |
| first_indexed | 2024-03-11T08:56:55Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-11T08:56:55Z |
| publishDate | 2023-02-01 |
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| series | Diagnostics |
| spelling | doaj.art-5f5a4279747f41c883bc59aef235c4d82023-11-16T20:02:43ZengMDPI AGDiagnostics2075-44182023-02-0113477010.3390/diagnostics13040770Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear ExaminationNamsu Kim0Tae Yun Kim1Ji Yoon Han2Joonhong Park3Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of KoreaDepartment of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of KoreaDepartment of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of KoreaBackground: Hereditary hemolytic anemia (HHA) is defined as a group of heterogeneous and rare diseases caused by defects of red blood cell (RBC) metabolism and RBC membrane, which leads to lysis or premature clearance. The aim of this study was to investigate individuals with HHA for potential disease-causing variants in 33 genes reported to be associated with HHA. Methods: A total of 14 independent individuals or families diagnosed with suspected HHA, and in particular, RBC membranopathy, RBC enzymopathy, and hemoglobinopathy, were collected after routine peripheral blood smear testing. A custom designed panel, including the 33 genes, was performed using gene panel sequencing on the Ion Torrent PGM™ Dx System. The best candidate disease-causing variants were confirmed by Sanger sequencing. Results: Several variants of the HHA-associated genes were detected in 10 out of 14 suspected HHA individuals. After excluding those variants predicted to be benign, 10 pathogenic variants and 1 variant of uncertain significance (VUS) were confirmed in 10 individuals with suspected HHA. Of these variants, the p.Trp704Ter nonsense variant of <i>EPB41</i> and missense p.Gly151Asp variant of <i>SPTA1</i> were identified in two out of four hereditary elliptocytoses. The frameshift p.Leu884GlyfsTer27 variant of <i>ANK1</i>, nonsense p.Trp652Ter variant of the <i>SPTB</i>, and missense p.Arg490Trp variant of <i>PKLR</i> were detected in all four hereditary spherocytosis cases. Missense p.Glu27Lys, nonsense p.Lys18Ter variants, and splicing errors such as c.92 + 1G > T and c.315 + 1G > A within <i>HBB</i> were identified in four beta thalassemia cases. Conclusions: This study provides a snapshot of the genetic alterations in a cohort of Korean HHA individuals and demonstrates the clinical utility of using gene panels in HHA. Genetic results can provide precise clinical diagnosis and guidance regarding medical treatment and management for some individuals.https://www.mdpi.com/2075-4418/13/4/770gene panel sequencinghereditary hemolytic anemia<i>ANK1</i> gene<i>EPB41</i> gene<i>SPTB</i> gene<i>HBB</i> gene |
| spellingShingle | Namsu Kim Tae Yun Kim Ji Yoon Han Joonhong Park Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination Diagnostics gene panel sequencing hereditary hemolytic anemia <i>ANK1</i> gene <i>EPB41</i> gene <i>SPTB</i> gene <i>HBB</i> gene |
| title | Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination |
| title_full | Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination |
| title_fullStr | Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination |
| title_full_unstemmed | Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination |
| title_short | Five Years’ Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination |
| title_sort | five years experience with gene panel sequencing in hereditary hemolytic anemia screened by routine peripheral blood smear examination |
| topic | gene panel sequencing hereditary hemolytic anemia <i>ANK1</i> gene <i>EPB41</i> gene <i>SPTB</i> gene <i>HBB</i> gene |
| url | https://www.mdpi.com/2075-4418/13/4/770 |
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