[摘要]目的分析1例Shwachman Diamond综合征(SDS)病人遗传学改变，探讨其与基因型表型的关系。方法提取1例SDS病儿的外周血全基因组DNA，纯化后经PCR扩增，利用二代测序技术对血液系统相关候选基因的全部编码区和侧翼剪切位点区域进行突变筛查，与人类基因组突变数据库中标准序列比对，寻找可疑突变位点，确定存在SBDS基因突变后，对病儿父母进行相同位点测序并进行一代测序验证。结果病儿15岁出现血常规异常，经骨髓穿刺诊断为骨髓增生异常综合征(MDS)，染色体G显带核型分析示46，XX，del20q-，后于16岁出现肾功能异常。二代测序结果显示病儿SBDS基因第2外显子剪切位点纯合突变：c.258+2Tgt;C，为纯合突变，其父母此位点均为杂合突变。此位点突变引起病儿SBDS基因mRNA在第2和第3外显子之间出现剪切错误，导致SBDS序列提前终止。结论本研究发现1例SDS病儿SBDS热点突变合并染色体20q-，为丰富基因型表型关系提供了依据。

    [关键词]骨髓增生异常-骨髓增殖性疾病;贫血，骨髓病性;寡核苷酸序列分析;突变;染色体畸变

    [中图分类号]R551.33[文献标志码]A[文章编号] 2096-5532(2018)06-0631-04

    SPLICE-SITE MUTATION AND PHENOTYPE IN SHWACHMAN-DIAMOND SYNDROME： AN ANALYSIS OF ONE CASE "WANG Fengqi， WEI Xiaonan， SHAO Cuihua， LIU Wenmiao， LIU Shiguo(Prenatal Diagnosis Center， the Affiliated Hospital of Qingdao University， Qingdao 266003， China)

    [ABSTRACT]ObjectiveTo explore the genetic changes of a patient with Shwachman-Diamond syndrome (SDS) and the relationship between genotype and phenotype. MethodsWhole genome DNA was extracted from the peripheral blood of a child with SDS. PCR amplification was performed after the DNA was purified. Next-generation sequencing was then applied to detect mutation in all the coding regions as well as splice sites in flanking regions of the candidate genes associated with the blood system. Then the sequencing data was compared with the standard sequence in the human gene mutation database to find the suspected mutation site. After determining the mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene ......