SEC23B基因突变诊断先天性红细胞生成异常性贫血Ⅱ型1例并文献复习

A case of diagnosis of congenital dyserythropoietic anemia Ⅱ with SEC23B gene mutation and the literature review

目的探讨分子生物学基因突变检测对于复杂、罕见遗传性疾病诊断的重要性,以提高对先天性红细胞生成异常性贫血(CDA)的认识。方法运用高通量二代测序技术对申请人进行血液系统疾病相关基因全外显子编码区及剪切区序列测定,在确定致病基因后,应用Sanger测序法进行验证,同时检测申请人父母的基因型。通过分析此病例资料并复习相关文献。结果申请人为年轻女性,成年后发现贫血、黄疸,脾大,胆囊结石,血象呈正细胞轻度贫血;血片可见6%球形红细胞;光镜下骨髓形态存在双核幼红细胞,以哑铃核、花核多见,偶见点彩,占有核红细胞的12%;申请人及其父母血液系统疾病基因筛查(高通量二代测序):申请人存在SEC23B基因c.74C>A(p.Pro25His)和c.1588C>T(p.Arg530Trp)复合杂合变异;其母存在SEC23B基因c.74C>A(p.Pro25His)杂合变异;其父存在SEC23B基因c.1588C>T(p.Arg530Trp)杂合变异。未行骨髓电镜、十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)检查。诊断为CDAⅡ型(CDAⅡ),因其未出现严重的铁过载等并发症,观察随访。结论 SEC23B基因c.74C>A(p.Pro25His)和c.1588C>T(p.Arg530Trp)复合杂合变异是本例CDAⅡ患者的可能分子发病机制,积极开展与该病相关的CDAN1、C150RF41、SEC23B、KIF23、KLF1和GATA1基因检测极为重要。

Objective To emphasize the importance of gene mutation detection in the diagnosis of complex and rare genetic diseases,and to enhance the understanding of congenital dyserythropoietic anemia(CDA).Methods High-throughput second-generation sequencing technology was used to identify the applicant′s hematopathy-related gene total exon coding and splicing sequence.After determining the pathogenic gene,utilized the Sanger sequencing method for verification,and the applicant,parents genotype were also tested.The case of CDAⅡ was reported and the related literatures were reviewed.Results The applicant was a young woman.When she was adult,she was found as anemia,jaundice,splenomegaly and gallbladder stone,and the blood routine showed mild anemia of normal cell.Blood smear showed 6% spherical red blood cells.Under the light microscope,there were dinuclear red blood cells in the form of bone marrow occupying 12%of nucleated red blood cells.The dumbbell nuclear and flower nuclear red blood cells were common,occasionally spotted nuclear were found.The blood system disease genetic screening(high-throughput second-generation sequencing)from applicant and her parents showed:the applicant had SEC23 Bgene c.74 C>A(p.Pro25 His)and c.1588 C>T(p.Arg530 Trp)complex heterozygous variation,and her mother had SEC23 Bgene c.74 C>A(p.Pro25 His)heterozygous variation and her father had SEC23 Bgene c.1588 C>T(p.Arg530 Trp)heterozygous variation.The applicant was diagnosised with CDAⅡ.and received follow-up for the time being because there were no complications such as severe iron overload.Conclusion The SEC23 B gene c.74 C> A(p.Pro25 His)and c.1588 C>T(p.Arg530 Trp)complex heterozygous variation is the molecular pathogenesis of this patient with CDAⅡ.To improve the understanding of CDA,it is extremely important to actively carry out the detection of CDAN1,C150 RF41,SEC23 B,KIF23,KLF1 and GATA1 gene related to the disease.