Genetic mutation analysis of hereditary spherocytosis in Guangxi Zhuang Autonomous Region
Tóm tắt
Hereditary spherocytosis (HS) is a common, hereditary hemolytic anemia (HHA) that is attributed to the disturbance of five erythrocyte membrane proteins. HS is also common in Guangxi, China. Target region capture high-throughput sequencing technology was used to analyze genetic mutations found in HS patients. Pedigree analysis was also performed, in some cases, to provide an optimized approach for the etiological diagnosis of complex, hereditary hemolytic anemia. Blood samples from the probands and their families were assessed by laboratory tests, target region capture high-throughput sequencing technology, and Sanger sequencing. We detected 79 HS patients from 37 unrelated families. The mutations observed in these patients were found mainly in four HS-related genes. These included SLC4A1, which was mutated in 31.65% of patients (25/79), SPTA1 (30.78% (24/79)), EPB42 (6.33% (5/79)), and SPTB (5.06% (4/79)). Composite genotype was observed in 26.58% (21/79) of patients and included mutations in two or more HS-related genes or mutations in HS-related genes combined with thalassemia or G6PD deficiency. No significant differences in clinical symptoms were found among patients of various genotypes except total bilirubin. Mean reticulocyte volume (MRV) and mean sphered cell volume (MSCV) of the composite genotype were significantly different from other groups. A total of 28 mutation types were found in HS-related genes. Using high-throughput sequencing technology, we also found some cases that had been misdiagnosed. MRV and MSCV are more significant in compound mutations as sensitive determinants of HS. High-throughput sequencing technology can be used to provide a more effective etiological diagnostic method for HS, with high efficiency and specificity.
Tài liệu tham khảo
Perrotta S, Gallagher PG, Mohandas N (2008) Hereditary spherocytosis. Lancet 372(9647):1411–1426. https://doi.org/10.1016/S0140-6736(08)61588-3
Iolascon A, Andolfo I, Barcellini W, Corcione F, Garçon L, De Franceschi L, Pignata C, Graziadei G, Pospisilova D, Rees DC, de Montalembert M, Rivella S, Gambale A, Russo R, Ribeiro L, Vives-Corrons J, Martinez PA, Kattamis A, Gulbis B, Cappellini MD, Roberts I, Tamary H, Working Study Group on Red Cells and Iron of the EHA (2017) Recommendations regarding splenectomy in hereditary hemolytic anemias. Haematologica. 102(8):1304–1283. https://doi.org/10.3324/haematol.2016.161166
Rizo-delaTorre LDC, Herrera-Tirado IM, Hernández-Peña R, Ibarra-Cortés B, Perea-Díaz FJ (2022) Hematological and molecular analysis of patients with G6PD deficiency revealed coexistent hereditary spherocytosis and alpha thalassemia. Ann Hum Genet 86(2):87–93. https://doi.org/10.1111/ahg.12451
Chen M, Ye YP, Liao L, Deng XL, Qiu YL, Lin FQ (2020) Hereditary spherocytosis overlooked for 7 years in a pediatric patient with β-thalassemia trait and novel compound heterozygous mutations of SPTA1 gene. Hematology 25(1):438–445. https://doi.org/10.1080/16078454.2020.1846874
Guitton C, Garçon L, Cynober T, Gauthier F, Tchernia G, Delaunay J, Leblanc T, Thuret I, Bader-Meunier B (2008) Sphérocytose héréditaire: recommandations pour le diagnostic et la prise en charge chez l’enfant [Hereditary spherocytosis: guidelines for the diagnosis and management in children]. Arch Pediatr 15(9):1464–73. French. https://doi.org/10.1016/j.arcped.2008.04.023.
Mariani M, Barcellini W, Vercellati C, Marcello AP, Fermo E, Pedotti P, Boschetti C, Zanella A (2008) Clinical and hematologic features of 300 patients affected by hereditary spherocytosis grouped according to the type of the membrane protein defect. Haematologica 93(9):1310–1317. https://doi.org/10.3324/haematol
Bianchi P, Fermo E, Vercellati C, Marcello AP, Porretti L, Cortelezzi A, Barcellini W, Zanella A (2012) Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and clinical characteristics. Haematologica 97(4):516–523. https://doi.org/10.3324/haematol.2011.052845
Liao L, Xu Y, Wei H, Qiu Y, Chen W, Huang J, Tao Y, Deng X, Deng Z, Tao H, Lin F (2019) Blood cell parameters for screening and diagnosis of hereditary spherocytosis. J Clin Lab Anal 33(4):e22844. https://doi.org/10.1002/jcla.22844
Xue J, He Q, Xie XJ, Su AL, Cao SB (2020) A clinical and experimental study of adult hereditary spherocytosis in the Chinese population. Kaohsiung J Med Sci 36(7):552–560. https://doi.org/10.1002/kjm2.12198
Jamwal M, Sharma P, Das R (2020) Laboratory approach to hemolytic anemia. Indian J Pediatr 87(1):66–74. https://doi.org/10.1007/s12098-019-03119-8
Vives-Corrons JL, Krishnevskaya E, Rodriguez IH, Ancochea A (2021) Characterization of hereditary red blood cell membranopathies using combined targeted next-generation sequencing and osmotic gradient ektacytometry. Int J Hematol 113(2):163–174. https://doi.org/10.1007/s12185-020-03010-9
Wang X, Zhang A, Huang M, Chen L, Hu Q, Lu Y, Cheng L (2020) Genetic and clinical characteristics of patients with hereditary spherocytosis in Hubei Province of China. Front Genet 18(11):953. https://doi.org/10.3389/fgene.2020.00953
Wu Y, Liao L, Lin F (2021) The diagnostic protocol for hereditary spherocytosis-2021 update. J Clin Lab Anal 35(12):e24034. https://doi.org/10.1002/jcla.24034
Wang R, Yang S, Xu M, Huang J, Liu H, Gu W, Zhang X (2018) Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci 61(8):947–953. https://doi.org/10.1007/s11427-017-9232-6
Yamamoto KS, Utshigisawa T, Ogura H, Aoki T, Kawakami T, Ohga S, Ohara A, Ito E, Yamamoto T, Kanno H (2022) Clinical and genetic diagnosis of thirteen Japanese patients with hereditary spherocytosis. Hum Genome Var 9(1):1. https://doi.org/10.1038/s41439-021-00179-1
Wang D, Song L, Shen L, Zhang K, Lv Y, Gao M, Ma J, Wan Y, Gai Z, Liu Y (2021) Mutational characteristics of causative genes in chinese hereditary spherocytosis patients: a report on fourteen cases and a review of the literature. Front Pharmacol 12:644352. https://doi.org/10.3389/fphar.2021.644352
Xie F, Lei L, Cai B, Gan L, Gao Y, Liu X, Zhou L, Jiang J (2021) Clinical manifestation and phenotypic analysis of novel gene mutation in 28 Chinese children with hereditary spherocytosis. Mol Genet Genomic Med. 9(4):e1577. https://doi.org/10.1002/mgg3.1577
Hao L, Li S, Ma D, Chen S, Zhang B, Xiao D, Zhang J, Jiang N, Jiang S, Ma J (2019) Two novel ANK1 loss-of-function mutations in Chinese families with hereditary spherocytosis. J Cell Mol Med 23(6):4454–4463. https://doi.org/10.1111/jcmm.14343
Kima ED, Mugnaini EN, Nava VE (2021) A novel SLC4A1 splice variant (c.2655+2_2655+3 del) in hereditary spherocytosis. Int J Lab Hematol 43(5):e242–e243. https://doi.org/10.1111/ijlh.13458
Chonat S, Risinger M, Sakthivel H, Niss O, Rothman JA, Hsieh L, Chou ST, Kwiatkowski JL, Khandros E, Gorman MF, Wells DT, Maghathe T, Dagaonkar N, Seu KG, Zhang K, Zhang W, Kalfa TA (2019) The spectrum of SPTA1-associated hereditary spherocytosis. Front Physiol 3(10):815. https://doi.org/10.3389/fphys.2019.00815
Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM (2013) Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N Engl J Med 369(16):1502–1511. https://doi.org/10.1056/NEJMoa1306555
Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, Das K, Toy T, Harry B, Yourshaw M, Fox M, Fogel BL, Martinez-Agosto JA, Wong DA, Chang VY, Shieh PB, Palmer CG, Dipple KM, Grody WW, Vilain E, Nelson SF (2014) Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 312(18):1880–1887. https://doi.org/10.1001/jama.2014.14604
Qin L, Nie Y, Zhang H, Chen L, Zhang D, Lin Y, Ru K (2020) Identification of new mutations in patients with hereditary spherocytosis by next-generation sequencing. J Hum Genet 65(4):427–434. https://doi.org/10.1038/s10038-020-0724-z
Tole S, Dhir P, Pugi J, Drury LJ, Butchart S, Fantauzzi M, Langer JC, Baker JM, Blanchette VS, Kirby-Allen M, Carcao MD (2020) Genotype-phenotype correlation in children with hereditary spherocytosis. Br J Haematol 191(3):486–496. https://doi.org/10.1111/bjh
Picard V, Guitton C, Thuret I, Rose C, Bendelac L, Ghazal K, Aguilar-Martinez P, Badens C, Barro C, Bénéteau C, Berger C, Cathébras P, Deconinck E, Delaunay J, Durand JM, Firah N, Galactéros F, Godeau B, Jaïs X, de Jaureguiberry JP, Le Stradic C, Lifermann F, Maffre R, Morin G, Perrin J, Proulle V, Ruivard M, Toutain F, Lahary A, Garçon L (2019) Clinical and biological features in PIEZO1-hereditary xerocytosis and Gardos channelopathy: a retrospective series of 126 patients. Haematologica 104(8):1554–1564. https://doi.org/10.3324/haematol.2018
Chen Y, Zhang S, Wang C, Chen S, Feng N, Liu H, Tang X, Wang J (2020) [Effect of high-throughput sequencing for the prevention and control of thalassemia]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 37(6):645–649. Chinese. https://doi.org/10.3760/cma.j.issn.1003-9406.
Aggarwal A, Jamwal M, Sharma P, Sachdeva MUS, Bansal D, Malhotra P, Das R (2020) Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next-generation sequencing: first South Asian study. Br J Haematol 188(5):784–795. https://doi.org/10.1111/bjh.16244
DeLoughery TG (2021) Anemia at altitude: Thalassemia, sickle cell disease, and other inherited anemias. High Alt Med Biol 22(2):113–118. https://doi.org/10.1089/ham