PDF(Pubmed)
Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：遗传性球形红细胞增多症（HS，MIM＃612641）是最常见的遗传性溶血性疾病之一。本研究旨在证实一种新的变异体的致病性，并揭示患者的遗传病因。
方法：回顾性分析1例在重庆医科大学附属儿童医院进行基因测序的HS患者的临床资料。然后对检测到的变体进行计算机预测和体外小基因剪接报告系统以分析其分子内影响。还提供了与由于SPTB基因变体引起的HS相关的文献的总结。
结果:在先证中鉴定了SPTB基因(NM_001024858.4)中的新变体(c.301-2A>G)。使用Sanger测序,我们最终证实，该变体的遗传不能追溯到亲生父母。体外小基因测定揭示了来自c.301-2A>G变体的三种不同转录本：r.301_474del，r.301_306delCCAAAAG,和r.301-1_301-57ins。通过文献综述,我们总结了已进行基因型验证的HS患者,并绘制了SPTB基因变异图谱.
结论：我们确定了SPTB基因的剪接变体，从而证实了其反常的翻译。新的变异是HS先证者的可能遗传病因。我们的发现扩展了SPTB基因的变异谱，从而从临床和分子角度提高对相关遗传性溶血性疾病的认识，为遗传咨询和诊断奠定基础。
方法：回顾性分析1例在重庆医科大学附属儿童医院进行基因测序的HS患者的临床资料。然后对检测到的变体进行计算机预测和体外小基因剪接报告系统以分析其分子内影响。还提供了与由于SPTB基因变体引起的HS相关的文献的总结。
结果:在先证中鉴定了SPTB基因(NM_001024858.4)中的新变体(c.301-2A>G)。使用Sanger测序,我们最终证实，该变体的遗传不能追溯到亲生父母。体外小基因测定揭示了来自c.301-2A>G变体的三种不同转录本：r.301_474del，r.301_306delCCAAAAG,和r.301-1_301-57ins。通过文献综述,我们总结了已进行基因型验证的HS患者,并绘制了SPTB基因变异图谱.
结论：我们确定了SPTB基因的剪接变体，从而证实了其反常的翻译。新的变异是HS先证者的可能遗传病因。我们的发现扩展了SPTB基因的变异谱，从而从临床和分子角度提高对相关遗传性溶血性疾病的认识，为遗传咨询和诊断奠定基础。
