Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte

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Choi, Hyoung Soo; Choi, Qute; Kim, Jung-Ah; Im, Kyong Ok; Park, Si Nae; Park, Yoomi; Shin, Hee Young; Kang, Hyoung Jin; Kook, Hoon; Kim, Seon Young; Kim, Soo-Jeong; Kim, Inho; Kim, Ji Yoon; Kim, Hawk; Park, Kyung Duki; Park, Kyung Bae; Park, Meerim; Park, Sang Kyu; Park, Eun Sil; Park, Jeong-A; Park, Jun Eun; Park, Ji Kyoung; Baek, Hee Jo; Seo, Jeong Ho; Shim, Ye Jee; Ahn, Hyo Seop; Yoo, Keon Hee; Yoon, Hoi Soo; Won, Young-Woong; Lee, Kun Soo; Lee, Kwang Chul; Lee, Mee Jeong; Lee, Sun Ah; Lee, Jun Ah; Lee, Jae Min; Lee, Jae Hee; Lee, Ji Won; Lim, Young Tak; Jung, Hyun Joo; Chueh, Hee Won; Choi, Eun Jin; Jung, Hye Lim; Kim, Ju Han; Lee, Dong Soon
Issue Date
BioMed Central
Orphanet Journal of Rare Diseases. 14(1):114
Hereditary spherocytosisRBC membrane disorderMolecular diagnosis
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.

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.

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.

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.
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College of Medicine/School of Medicine (의과대학/대학원)Laboratory Medicine (검사의학전공)Journal Papers (저널논문_검사의학전공)
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