A novel essential splice site variant in SPTB in a large hereditary spherocytosis family.

Autor: Nieminen TT; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., Liyanarachchi S; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., Comiskey DF Jr; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., Wang Y; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., Li W; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., Hendrickson IV; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., Brock P; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA., de la Chapelle A; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., He H; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2021 May; Vol. 9 (5), pp. e1641. Date of Electronic Publication: 2021 May 04.
DOI: 10.1002/mgg3.1641
Abstrakt: Background: We studied a large family with 22 individuals affected with autosomal dominant hereditary spherocytosis (HS).
Methods: Genome-wide linkage, whole-genome sequencing (WGS), Sanger sequencing, RT-PCR, and ToPO TA cloning analyses were performed.
Results: We revealed a heterozygous G>A transition in the 14q23 locus, at position +1 of the intron 8 donor splice site of the spectrin beta, erythrocytic (SPTB) gene. This splice variant (SPTB c.1064+1G>A) was confirmed by Sanger sequencing and showed complete co-segregation with HS in the family. Further RT-PCR reactions and sequencing analysis indicated that the variant leads to the exclusion of exon 8 and subsequent frameshift in exon 9 and a premature stop codon in SPTB. Translation of the altered allele would lead to a truncation with a loss of all spectrin repeat domains in SPTB protein.
Conclusion: This variant is novel and has not been found in any databases. We propose that this splice variant explains the spherocytosis phenotype observed in this large family.
(© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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