Pei-Chin Lin1, Shyh-Shin Chiou1, Chien-Yu Lin2, Shu-Chen Wang3, Hsi-Yuan Huang4, Ya-Sian Chang5, Yu-Hsin Tseng6, Tzu-Min Kan6, Yu-Mei Liao7, Shih-Pien Tsai8, Ching-Tien Peng9, Jan-Gowth Chang10. 1. Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 2. Department of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan. 3. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 4. Department of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. 5. Department of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan. 6. Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 7. Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 8. Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 9. Department of Pediatrics, China Medical University Children's Hospital, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan. Electronic address: pct@mail.cmuh.org.tw. 10. Department of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan; Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan; Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan. Electronic address: d6781@mail.cmuh.org.tw.
Abstract
PURPOSE: Congenital hemolytic anemia caused by red blood cell (RBC) membrane defects is a heterogeneous group of disorders. The present study aimed to search the causative gene mutations in patients with RBC membrane disorders in Taiwan. MATERIALS AND METHODS: Next-generation sequencing approach using whole-exome sequencing (WES) was performed. Sanger sequencing was performed for confirmation of variants detected in WES in patients and their family members. RESULTS: Five causative variants, including two ANK1, two SPTA and one SPTB variants, were detected in four patients. All these variants, except one SPTA1 variant c.83G > A (p.R28H), are novel variants. Their pedigree analysis showed one de novo SPTA1 mutation c.83G > A (p.R28H) combined with αLELY, one de novo ANK1 mutation c.1034C > A (p.A345E), one autosomal dominant combined SPTA1 c.4604A > C (p.Q1535P) and SPTB c.6203 T > C (p.L2068P) mutations and one autosomal dominant ANK1 c.4462C > T (p.R1488X) mutation. CONCLUSIONS: Our data demonstrated that WES is an efficient tool for determining genetic etiologies of RBC membrane disorders and can facilitate accurate diagnosis and genetic counseling. Additional studies should be conducted on larger cohorts to investigate the distribution of gene mutations in patients with RBC membrane disorders in Taiwan.
PURPOSE:Congenital hemolytic anemia caused by red blood cell (RBC) membrane defects is a heterogeneous group of disorders. The present study aimed to search the causative gene mutations in patients with RBC membrane disorders in Taiwan. MATERIALS AND METHODS: Next-generation sequencing approach using whole-exome sequencing (WES) was performed. Sanger sequencing was performed for confirmation of variants detected in WES in patients and their family members. RESULTS: Five causative variants, including two ANK1, two SPTA and one SPTB variants, were detected in four patients. All these variants, except one SPTA1 variant c.83G > A (p.R28H), are novel variants. Their pedigree analysis showed one de novo SPTA1 mutation c.83G > A (p.R28H) combined with αLELY, one de novo ANK1 mutation c.1034C > A (p.A345E), one autosomal dominant combined SPTA1 c.4604A > C (p.Q1535P) and SPTB c.6203 T > C (p.L2068P) mutations and one autosomal dominant ANK1 c.4462C > T (p.R1488X) mutation. CONCLUSIONS: Our data demonstrated that WES is an efficient tool for determining genetic etiologies of RBC membrane disorders and can facilitate accurate diagnosis and genetic counseling. Additional studies should be conducted on larger cohorts to investigate the distribution of gene mutations in patients with RBC membrane disorders in Taiwan.