A novel variant in the <i>SPTB</i> gene underlying hereditary spherocytosis and a literature review of previous variants

作者全名："Wang, Yang; Liu, Tao; Jia, Chenxi; Xiao, Li; Wang, Wen; Zhang, Yongjie; Xiang, Yan; Huang, Lan; Yu, Jie"

作者地址："[Wang, Yang; Liu, Tao; Xiao, Li; Zhang, Yongjie; Xiang, Yan; Huang, Lan; Yu, Jie] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Dept Hem, 136 Zhongshanerlu, Chongqing 400014, Peoples R China; [Jia, Chenxi] Chongqing Key Lab Struct Birth Defect & Reconstruc, Chongqing, Peoples R China; [Wang, Wen] Shanghai Univ Med & Hlth Sci, Shanghai, Peoples R China"

通信作者："Yu, J (通讯作者)，Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Dept Hem, 136 Zhongshanerlu, Chongqing 400014, Peoples R China."

来源：BMC MEDICAL GENOMICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001294077200002

JCR分区：Q2

影响因子：2.7

年份：2024

卷号：17

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Novel variant; Hereditary spherocytosis; SPTB gene; Minigene

摘要："Background Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant's pathogenicity and reveal a patient's genetic etiology. Methods The clinical data of a patient with HS who underwent genetic sequencing at the Children's Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. Results A novel variant (c.301-2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301-2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. Conclusion We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis."

基金机构：Public Welfare Project for Rare Blood Disorders in the field of Hematology in China

基金资助正文："We express our gratitude for the contribution made by the patients, their families, pediatricians, and investigators. We thank Mengxue Gao for his guidance and assistance in bringing forth the figures. We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript."