摘要
目的 探讨一例3M综合征合并Netherton综合征胎儿的基因诊断及索源过程。方法 胎儿27周行脐静脉穿刺术,脐血及其父母血液提取gDNA,进行家系全外显子组测序,对发现的基因变异位点进行Sanger测序验证。结果 超声影像检查提示胎儿特殊面容、生长发育迟缓。胎儿CUL7基因存在复合杂合致病变异,变异1:c.3291_3294delTCAC(p.His1098Cysfs*42)杂合变异,父亲野生型,母亲杂合型;变异2:c.4717C>T(p.Arg1573*)杂合变异,父亲杂合型,母亲野生型,符合3M综合征Ⅰ型基因型。胎儿SPINK5基因存在复合杂合变异,变异1:c.2474_2475delAG(p.Glu825Glyfs*2)杂合致病变异,父亲杂合型,母亲野生型;变异2:c.2870delT(p.Leu957Gln*46)杂合变异,可能致病,父亲野生型,母亲杂合型,符合Netherton综合征基因型。结论 胎儿为3M综合征合并Netherton综合征,CUL7基因c.3291_3294delTCAC与SPINK5基因c.2870delT两个变异为首次报道。对超声影像筛查提示胎儿结构畸形推荐进行家系外显子组测序以早期明确诊断,实现优生优育。
Objective To analyze a case of a fetus with 3M syndrome and Netherton syndrome and then research the origin of genes variants. Methods An cordocentesis was done at 27 weeks after the consent. The trio whole exome sequencing analyses were performed by Roche KAPA HyperExome and BGI MGISEQ sequencer,the mutant genes were validated by Sanger sequencing. Results The fetus was detected by prenatal ultrasound screening with a special face and retardation of growth. There were two variants in the CUL7 gene,Variant 1:c.3291_3294delTCAC(p.His1098Cysfs*42),pathogenic,with wild type of father and heterozygous of mother. Variant 2:c.4717C>T(p.Arg1573*),pathogenic,with heterozygous of father and wild type of mother. There were also two variants in the SPINK5 gene,Variant 1:c.2474_2475delAG(p.Glu825Glyfs*2),pathogenic,with heterozygous of father and wild type of mother. Variant 2:c.2870delT(p.Leu957Gln*46),likely pathogenic,with wild type of father and heterozygous of mother. Conclusion The fetus was diagnosed as 3M syndrome and Netherton syndrome,the CUL7;c.3291_3294delTCAC and the SPINK5;c.2870delT were de novo mutations. For the case of structural abnormalities detected by prenatal ultrasound screening,the trio whole exome sequencing is a recommended effective diagnostic method.
作者
黎伟豪
黄秀静
叶燕绸
LI Weihao;HUANG Xiujing;YE Yanchou(Reproductive Medicine Center,the Seventh Affiliated Hospital Sun Yat-sen University,Shenzhen,Guangdong,China,518107;Department of Obstetrics and Gynecology,the Seventh Affiliated Hospital,Sun Yat-sen University,Shenzhen,Guangdong,China,518107)
出处
《分子诊断与治疗杂志》
2022年第11期2009-2013,共5页
Journal of Molecular Diagnostics and Therapy
