RPS6KA3基因变异所致Coffin-Lowry综合征的分子诊断及家系遗传分析  

Molecular diagnosis and pedigree analysis of Coffin-Lowry syndrome caused by RPS6K A3 gene variation

作　　者：刘渊[1] 曾玉坤[1] 刘玲[1] 黄演林[1] 余丽华[1] 丁红珂[1] Liu Yuan;Zeng Yukun;Liu Ling;Huang Yanlin;Yu Lihua;Ding Hongke(Guangdong Women and Children Hos pital,Guangzhou 511442,Guangdong,China)

机构地区：[1]广东省妇幼保健院医学遗传中心,广东广州511442

出　　处：《中国产前诊断杂志（电子版）》2021年第3期34-39,共6页Chinese Journal of Prenatal Diagnosis(Electronic Version)

基　　金：广州市科技局基础与应用基础研究项目(202102080263)。

摘　　要：目的 利用二代测序技术分析Coffin-Lowry综合征致病基因,为先证者家庭再妊娠提供遗传咨询和产前诊断分析。方法 以2020年来广东省妇幼保健院就诊的2例Coffin-Lowry综合征家系为研究对象,利用高通量测序技术检测先证者的致病基因,对变异位置设计引物后进行PCR实验和Sanger测序,同时验证先证者父母基因型,并进一步结合基因诊断结果对家系再次妊娠进行产前评估及分子诊断。结果 高通量测序发现2个先证者的RPS6 KA3基因均存在致病变异位点,分别为c.1672C>T(p.R558*)和(c.325+2_325+3insT)半合子变异,一代测序验证显示先证者父母均未检测到相同变异,判断先证者RPS6 KA3基因为新发变异。对2个家系再次妊娠进行产前评估及分子诊断,结果未发现存在与先证者相同变异。结论 本研究采用高通量测序成功对Coffin-Lowry综合征患者进行了分子诊断,所检测的变异均为中国人群首次报道。先证者均为新发变异,符合该综合征的发病模式,为该家庭提供了精确的分子诊断和再次妊娠的产前遗传咨询信息。Objective To detect the variants in RPS6KA3 gene in patients with Coffin-Lowry syndrome(CLS)by using next-generation sequencing technology and provide genetic counseling and prenatal diagnosis for two unrelated families.Methods Two patients with CLS were referred to our center for genetic counseling.By using next-generation sequencing technology(NGS),we found 2 variants in RPS6 KA3 gene in these two patients.Primers were designed for polymerase chain reaction(PCR)experiments.Sanger sequencing validations for the variants of RPS6 KA3 in the proband’s parents were performed.Results Two pathogenic heterozygous variants were found in RPS6KA3 gene in the two probands,which were c.1672 C>T(p.R558*)and(c.325+2325+3 insT),respectively.Sanger sequencing validations showed their parents were normal which indicated the pathogenic heterozygous variants were de novo variants.Furthermore,the analysis of prenatal molecular diagnosis showed the current fetus did not have the same mutation with probands.Conclusion By using next-generation sequencing technology,we successfully identified two de novo variants in two unrelated families.Base on the prenatal invasive analysis,these two families received precise molecular diagnosis and prenatal genetic counseling for their current pregnancies.

关 键 词：Coffin-Lowry综合征 RPS6 KA3 高通量测序 产前诊断 

分 类 号：R714.55[医药卫生—妇产科学]