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Novel compound heterozygous mutations in the SPTA1 gene, causing hereditary spherocytosis in a neonate with Coombs‑negative hemolytic jaundice.
Mol Med Rep. 2019 Apr; 19(4):2801-2807.MM

Abstract

Hereditary spherocytosis (HS) is a common heterogeneous type of inherited hemolytic anemia characterized by jaundice and splenomegaly. Diagnosis of HS in neonates is considered unreliable, and is generally based on positive family history, spherocytes in peripheral smears, increased osmotic fragility, and jaundice. In the present study, routine laboratory tests, next‑generation sequencing, and Sanger sequencing were applied to diagnose a neonatal patient with Coombs‑negative hemolytic jaundice. The neonate had no family history of HS; however, spherocytes were observed in peripheral smears, and the patient exhibited Coombs‑negative and severe hemolytic jaundice, normal mean corpuscular hemoglobin concentration (MCHC) and mean corpuscular volume (MCV), normal glucose‑6‑phosphate dehydrogenase activity, negative thalassemia genetic mutation screening results, and negative autoimmune antibody tests. Novel compound heterozygous mutations in the spectrin‑α, erythrocytic 1 (SPTA1) gene (c.3897‑1G>C and c.5029G>A) were identified. The SPTA1 c.3897‑1G>C mutation in intron 27‑1, which disrupted the consensus splice site, was inherited from his asymptomatic mother, and the SPTA1 c.5029G>A (p.Gly1677Arg) mutation in trans with the SPTA1 c.3897‑1G>C mutation was inherited from his asymptomatic father. Sanger sequencing of mRNA reverse transcribed into cDNA identified a deletion of the first 10 nucleotides of exon 28, confirming the splicing mutation. In conclusion, the present study reports a rare case of autosomal‑recessive HS with a severe clinical phenotype, but normal MCHC and MCV.

Authors+Show Affiliations

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

30816434

Citation

Wang, Xiong, et al. "Novel Compound Heterozygous Mutations in the SPTA1 Gene, Causing Hereditary Spherocytosis in a Neonate With Coombs‑negative Hemolytic Jaundice." Molecular Medicine Reports, vol. 19, no. 4, 2019, pp. 2801-2807.
Wang X, Liu A, Lu Y, et al. Novel compound heterozygous mutations in the SPTA1 gene, causing hereditary spherocytosis in a neonate with Coombs‑negative hemolytic jaundice. Mol Med Rep. 2019;19(4):2801-2807.
Wang, X., Liu, A., Lu, Y., & Hu, Q. (2019). Novel compound heterozygous mutations in the SPTA1 gene, causing hereditary spherocytosis in a neonate with Coombs‑negative hemolytic jaundice. Molecular Medicine Reports, 19(4), 2801-2807. https://doi.org/10.3892/mmr.2019.9947
Wang X, et al. Novel Compound Heterozygous Mutations in the SPTA1 Gene, Causing Hereditary Spherocytosis in a Neonate With Coombs‑negative Hemolytic Jaundice. Mol Med Rep. 2019;19(4):2801-2807. PubMed PMID: 30816434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel compound heterozygous mutations in the SPTA1 gene, causing hereditary spherocytosis in a neonate with Coombs‑negative hemolytic jaundice. AU - Wang,Xiong, AU - Liu,Aiguo, AU - Lu,Yanjun, AU - Hu,Qun, Y1 - 2019/02/08/ PY - 2018/06/29/received PY - 2019/02/06/accepted PY - 2019/3/1/pubmed PY - 2019/8/2/medline PY - 2019/3/1/entrez SP - 2801 EP - 2807 JF - Molecular medicine reports JO - Mol Med Rep VL - 19 IS - 4 N2 - Hereditary spherocytosis (HS) is a common heterogeneous type of inherited hemolytic anemia characterized by jaundice and splenomegaly. Diagnosis of HS in neonates is considered unreliable, and is generally based on positive family history, spherocytes in peripheral smears, increased osmotic fragility, and jaundice. In the present study, routine laboratory tests, next‑generation sequencing, and Sanger sequencing were applied to diagnose a neonatal patient with Coombs‑negative hemolytic jaundice. The neonate had no family history of HS; however, spherocytes were observed in peripheral smears, and the patient exhibited Coombs‑negative and severe hemolytic jaundice, normal mean corpuscular hemoglobin concentration (MCHC) and mean corpuscular volume (MCV), normal glucose‑6‑phosphate dehydrogenase activity, negative thalassemia genetic mutation screening results, and negative autoimmune antibody tests. Novel compound heterozygous mutations in the spectrin‑α, erythrocytic 1 (SPTA1) gene (c.3897‑1G>C and c.5029G>A) were identified. The SPTA1 c.3897‑1G>C mutation in intron 27‑1, which disrupted the consensus splice site, was inherited from his asymptomatic mother, and the SPTA1 c.5029G>A (p.Gly1677Arg) mutation in trans with the SPTA1 c.3897‑1G>C mutation was inherited from his asymptomatic father. Sanger sequencing of mRNA reverse transcribed into cDNA identified a deletion of the first 10 nucleotides of exon 28, confirming the splicing mutation. In conclusion, the present study reports a rare case of autosomal‑recessive HS with a severe clinical phenotype, but normal MCHC and MCV. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/30816434/Novel_compound_heterozygous_mutations_in_the_SPTA1_gene_causing_hereditary_spherocytosis_in_a_neonate_with_Coombs‑negative_hemolytic_jaundice_ L2 - http://www.spandidos-publications.com/mmr/19/4/2801 DB - PRIME DP - Unbound Medicine ER -