A novel SPTB gene mutation in neonatal hereditary spherocytosis: A case report

Liu,Yang; Zheng,Jie; Song,Li; Fang,Yulian; Sun,Chao; Li,Na; Liu,Geli; Shu,Jianbo

doi:10.3892/etm.2020.9062

A novel SPTB gene mutation in neonatal hereditary spherocytosis: A case report

Authors:
- Yang Liu
- Jie Zheng
- Li Song
- Yulian Fang
- Chao Sun
- Na Li
- Geli Liu
- Jianbo Shu
View Affiliations

Affiliations: Department of Neonatalogy, Tianjin Children's Hospital, The Pediatric Clinical College in Tianjin Medical University, Tianjin 300074, P.R. China, Graduate College of Tianjin Medical University, Tianjin 300070, P.R. China, Tianjin Key Laboratory of Prevention and Treatment of Birth Defects, Tianjin 300134, P.R. China, Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: July 28, 2020 https://doi.org/10.3892/etm.2020.9062
Pages: 3253-3259
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to enhance the understanding of the diagnosis and treatment of neonatal hereditary spherocytosis (HS). Gene sequencing and analysis was performed for the crucial splicing signals on the exons and introns of the 302 known pathogenic genes [including ANK1, SPTAN1, SPTA1, EPB42, SLC4A1, and SPTB] that are associated with this genetic deficiency of erythrocytes. A 26‑day‑old female presented with jaundice, anemia, an increased count in peripheral blood reticulocyte and spherocytes and a positive acidified glycerol hemolysis test. Gene sequencing revealed a novel mutation of c.3737delA (p.Lys1246fs) in the exon 16 of SPTB (14q23|NM_000347.5) gene in the patient and her father. The mutation was a frame‑shifting mutation, which may result in the truncation of β‑haemoglobin in the erythrocyte membrane can lead to loss of normal function, leading to the occurrence of diseases, including jaundice and hemolytic anemia. For neonates with jaundice and anemia, family history, erythrocyte index and peripheral blood smear findings have been indicated to contribute to the diagnosis of HS. In the current study, gene sequencing was indicated to be helpful for the diagnosis of HS. A novel mutation of SPTB gene was identified, which may be pathogenic via modulating the activity of β‑spectrin in the erythrocyte membrane.

View Figures

View References

1	Tole S, Dhir P, Pugi J, Drury LJ, Butchart S, Fantauzzi M, Langer JC, Baker JM, Blanchette VS, Kirby-Allen M and Carcao MD: Genotype-phenotype correlation in children with hereditary spherocytosis. Br J Haematol: May 20, 2020 (Epub ahead of print).
2	Wang C, Cui Y, Li Y, Liu X and Han J: A systematic review of hereditary spherocytosis reported in Chinese biomedical journals from 1978 to 2013 and estimation of the prevalence of the disease using a disease model. Intractable Rare Dis Res. 4:76–81. 2015.PubMed/NCBI View Article : Google Scholar
3	Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG and Julian BA: The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 22:1795–1803. 2011.PubMed/NCBI View Article : Google Scholar
4	Da Costa L, Suner L, Galimand J, Bonnel A, Pascreau T, Couque N, Fenneteau O and Mohandas N: Society of Hematology and Pediatric Immunology (SHIP) group; French Society of Hematology (SFH). Diagnostic tool for red blood cell membrane disorders: Assessment of a new generation ektacytometer. Blood Cells Mol Dis. 56:9–22. 2016.PubMed/NCBI View Article : Google Scholar
5	Perrotta S, Gallagher PG and Mohandas N: Hereditary spherocytosis. Lancet. 372:1411–1426. 2008.PubMed/NCBI View Article : Google Scholar
6	Bolton-Maggs PH, Langer JC, Iolascon A, Tittensor P and King MJ: General Haematology Task Force of the British Committee for Standards in Haematology. Guidelines for the diagnosis and management of hereditary spherocytosis-2011 update. Br J Haematol. 156:37–49. 2012.PubMed/NCBI View Article : Google Scholar
7	Manciu S, Matei E and Trandafir B: Hereditary spherocytosis-diagnosis, surgical treatment and outcomes. A literature Review. Chirurgia (Bucur). 112:110–116. 2017.PubMed/NCBI View Article : Google Scholar
8	Zong XN and Li H: Construction of a new growth references for China based on urban Chinese children: Comparison with the WHO growth standards. PLoS One. 8(e59569)2013.PubMed/NCBI View Article : Google Scholar
9	Li H and Durbin R: Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 25:1754–1760. 2009.PubMed/NCBI View Article : Google Scholar
10	Wang K, Li M and Hakonarson H: ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38(e164)2010.PubMed/NCBI View Article : Google Scholar
11	Andolfo I, Russo R, Gambale A and Iolascon A: New insights on hereditary erythrocyte membrane defects. Haematologica. 101:1284–1294. 2016.PubMed/NCBI View Article : Google Scholar
12	Farias MG: Advances in laboratory diagnosis of hereditary spherocytosis. Clin Chem Lab Med. 55:944–948. 2017.PubMed/NCBI View Article : Google Scholar
13	He BJ, Liao L, Deng ZF, Tao YF, Xu YC and Lin FQ: Molecular genetic mechanisms of hereditary spherocytosis: Current perspectives. Acta Haematol. 139:60–66. 2018.PubMed/NCBI View Article : Google Scholar
14	Wang X, Liu A, Lu Y and Hu Q: Novel compound heterozygous mutations in the SPTA1 gene, causing hereditary spherocytosis in a neonate with Coombsnegative hemolytic jaundice. Mol Med Rep. 19:2801–2807. 2019.PubMed/NCBI View Article : Google Scholar
15	King MJ, Garcon L, Hoyer JD, Iolascon A, Picard V, Stewart G, Bianchi P, Lee SH and Zanella A: International Council for Standardization in Haematology. ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders. Int J Lab Hematol. 37:304–325. 2015.PubMed/NCBI View Article : Google Scholar
16	Christensen RD, Yaish HM and Gallagher PG: A pediatrician's practical guide to diagnosing and treating hereditary spherocytosis in neonates. Pediatrics. 135:1107–1114. 2015.PubMed/NCBI View Article : Google Scholar
17	Christensen RD, Nussenzveig RH, Yaish HM, Henry E, Eggert LD and Agarwal AM: Causes of hemolysis in neonates with extreme hyperbilirubinemia. J Perinatol. 34:616–619. 2014.PubMed/NCBI View Article : Google Scholar
18	Da Costa L, Galimand J, Fenneteau O and Mohandas N: Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev. 27:167–178. 2013.PubMed/NCBI View Article : Google Scholar
19	Llaudet-Planas E, Vives-Corrons JL, Rizzuto V, Gómez-Ramírez P, Sevilla Navarro J, Coll Sibina MT, García-Bernal M, Ruiz Llobet A, Badell I, Velasco-Puyó P, et al: Osmotic gradient ektacytometry: A valuable screening test for hereditary spherocytosis and other red blood cell membrane disorders. Int J Lab Hematol. 40:94–102. 2018.PubMed/NCBI View Article : Google Scholar
20	Park SH, Park CJ, Lee BR, Cho YU, Jang S, Kim N, Koh KN, Im HJ, Seo JJ, Park ES, et al: Comparison study of the eosin-5'-maleimide binding test, flow cytometric osmotic fragility test, and cryohemolysis test in the diagnosis of hereditary spherocytosis. Am J Clin Pathol. 142:474–484. 2014.PubMed/NCBI View Article : Google Scholar
21	Baloira A, Bastos M, Pousada G and Valverde D: Pulmonary arterial hypertension associated with hereditary spherocytosis and splenectomy in a patient with a mutation in the BMPR2 gene. Clin Case Rep. 4:752–755. 2016.PubMed/NCBI View Article : Google Scholar
22	Bader-Meunier B, Gauthier F, Archambaud F, Cynober T, Mielot F, Dommergues JP, Warszawski J, Mohandas N and Tchernia G: Long-term evaluation of the beneficial effect of subtotal splenectomy for management of hereditary spherocytosis. Blood. 97:399–403. 2001.PubMed/NCBI View Article : Google Scholar
23	Abdullah F, Zhang Y, Camp M, Rossberg MI, Bathurst MA, Colombani PM, Casella JF, Nabaweesi R and Chang DC: Splenectomy in hereditary spherocytosis: Review of 1,657 patients and application of the pediatric quality indicators. Pediatr Blood Cancer. 52:834–837. 2009.PubMed/NCBI View Article : Google Scholar
24	Guizzetti L: Total versus partial splenectomy in pediatric hereditary spherocytosis: A systematic review and meta-analysis. Pediatr Blood Cancer. 63:1713–1722. 2016.PubMed/NCBI View Article : Google Scholar
25	Fan LL, Liu JS, Huang H, Du R and Xiang R: Whole exome sequencing identified a novel mutation (p.Ala1884Pro) of β-spectrin in a Chinese family with hereditary spherocytosis. J Gene Med. 21(e3073)2019.PubMed/NCBI View Article : Google Scholar
26	Boguslawska DM, Heger E, Machnicka B, Skulski M, Kuliczkowski K and Sikorski AF: A new frameshift mutation of the β-spectrin gene associated with hereditary spherocytosis. Ann Hematol. 96:163–165. 2017.PubMed/NCBI View Article : Google Scholar
27	Shin S, Jang W, Kim M, Kim Y, Park SY, Park J and Yang YJ: Targeted next-generation sequencing identifies a novel nonsense mutation in SPTB for hereditary spherocytosis: A case report of a Korean family. Medicine (Baltimore). 97(e9677)2018.PubMed/NCBI View Article : Google Scholar
28	van Vuren A, van der Zwaag B, Huisjes R, Lak N, Bierings M, Gerritsen E, van Beers E, Bartels M and van Wijk R: The complexity of genotype-phenotype correlations in hereditary spherocytosis: A Cohort of 95 Patients: Genotype-phenotype correlation in hereditary spherocytosis. Hemasphere. 3(e276)2019.PubMed/NCBI View Article : Google Scholar
29	Maciag M, Plochocka D, Adamowicz-Salach A and Burzynska B: Novel beta-spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA. Br J Haematol. 146:326–332. 2009.PubMed/NCBI View Article : Google Scholar
30	Barcellini W, Bianchi P, Fermo E, Imperiali FG, Marcello AP, Vercellati C, Zaninoni A and Zanella A: Hereditary red cell membrane defects: Diagnostic and clinical aspects. Blood Transfus. 9:274–277. 2011.PubMed/NCBI View Article : Google Scholar
31	Iolascon A and Avvisati RA: Genotype/phenotype correlation in hereditary spherocytosis. Haematologica. 93:1283–1288. 2008.PubMed/NCBI View Article : Google Scholar
32	Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, et al: SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res. 46:W296–W303. 2018.PubMed/NCBI View Article : Google Scholar
33	Park J, Jeong DC, Yoo J, Jang W, Chae H, Kim J, Kwon A, Choi H, Lee JW, Chung NG, et al: Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis. Clin Genet. 90:69–78. 2016.PubMed/NCBI View Article : Google Scholar
34	Wang R, Yang S, Xu M, Huang J, Liu H, Gu W and Zhang X: Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 61:947–953. 2018.PubMed/NCBI View Article : Google Scholar
35	Xue J, He Q, Xie X, Su A and Cao S: Erratum to clinical utility of targeted gene enrichment and sequencing technique in the diagnosis of adult hereditary spherocytosis. Ann Transl Med. 7(S391)2019.PubMed/NCBI View Article : Google Scholar
36	Qin L, Nie Y, Zhang H, Chen L, Zhang D, Lin Y and Ru K: Identification of new mutations in patients with hereditary spherocytosis by next-generation sequencing. J Hum Genet. 65:427–434. 2020.PubMed/NCBI View Article : Google Scholar