Objective: To investigate the clinical and genetic characteristics of a family with hereditary spherocytosis (HS), to clarify the cause of the disease, and to provide the basis for genetic counseling and prenatal diagnosis.
Methods: The clinical data of proband and his parents were collected, and HS-related pathogenic genovariation of the proband was detected by high throughput sequencing. Suspected pathogenic mutation sites were verified by PCR-Sanger sequencing, and the fetus were conceived by a proband mother underwent prenatal diagnosis.
Results: Clinical manifestations of the proband showed moderate anemia, mild splenomegaly, and jaundice (an indirect increase of bilirubin). The gene detection showed that the proband showed compound heterozygous mutations of SPTB gene c. 6095T > C (p.Leu2032Pro) and c. 6224A > G (p.Glu2075Gly), which was inherited from the asymptomatic mother and father, respectively. Both mutations were detected rarely in the common population. Prenatal diagnosis revealed that the fetus inherited a mutant gene of the mother.
Conclusion: The compound heterozygous mutations of SPTB genes c.6095T>C (p.Leu2032Pro) and c.6224A>G (p.Glu2075Gly) were the causes of the family disease, which provides a basis for family genetic counseling and prenatal diagnosis. This report is the first one found in the HGMD,1000G and EXAC database, which provides an addition to the mutation profile of the SPTB gene.
题目: SPTB基因新型复合杂合突变致遗传性球形红细胞增多症遗传学分析及产前诊断.
目的: 探讨一个遗传性球形红细胞增多症（HS）家系的临床及遗传学特征，明确其致病原因并为遗传咨询和产前诊断提供依据.
方法: 收集家系成员的临床资料，应用高通量测序的方法检测先证者HS相关致病基因变异情况，采用PCR-Sanger测序法对疑似致病突变位点进行家系验证，对先证者母亲所妊娠的胎儿行产前诊断.
结果: 先证者临床表现为中度贫血、轻度脾肿大和黄疸。基因检测发现，先证者存在SPTB基因c.6095T>C(p.Leu2032Pro)和c.6224A>G(p.Glu2075Gly)复合杂合突变，分别遗传自无临床表现的母亲、父亲，这2个突变位点在正常人群中发生频率极低。产前诊断结果显示胎儿遗传了母亲的突变基因.
结论: SPTB基因c.6095T>C(p.Leu2032Pro)和c.6224A>G（p.Glu2075Gly）复合杂合突变为该HS家系的致病原因，为遗传咨询和产前诊断提供了依据。经查HGMD、1000G和EXAC数据库这两个突变位点均为首次报道，丰富了SPTB基因突变谱.
Keywords: SPTB gene; hereditary spherocytosis; new mutation; prenatal diagnosis.