3同胞的不同遗传缺陷及产前诊断研究  

Different genetic defects and prenatal diagnosis of three siblings

作　　者：马雪 陈哲晖 宋金青[1] 董慧[1] 金颖[1] 李梦秋 孔元原[2] 杨艳玲[1] Ma Xue;Chen Zhehui;Song Jinqing;Dong Hui;Jin Ying;Li Mengqiu;Kong Yuanyuan;Yang Yanling(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Department of Newborn Screening,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing 100026,China)

机构地区：[1]北京大学第一医院儿科,北京100034 [2]首都医科大学附属北京妇产医院新生儿筛查中心,北京100026

出　　处：《兰州大学学报（医学版）》2023年第4期66-70,共5页Journal of Lanzhou University（Medical Sciences）

基　　金：国家重点研发计划资助项目(2022YFC2703401,2019YFC1005100)。

摘　　要：目的通过对3同胞不同遗传缺陷的诊断及干预,探讨遗传咨询及产前诊断策略。方法采用生化、基因及染色体分析明确诊断,通过羊水细胞基因分析对第3胎进行产前诊断。结果先证者,男,2月龄时因发育落后就诊,血液苯丙氨酸>1200μmol/L,PAH基因检出已知致病变异c.728G>A及c.1068C>A,确诊为经典型苯丙酮尿症(PKU),经规范低苯丙氨酸饮食治疗后血液苯丙氨酸浓度控制良好,3月龄后出现难治性癫痫,重度智力损害,14岁时死亡。母亲第2胎孕中期发现胎儿脐膨出,羊水细胞染色体核型异常[45,XN,-21(3)/46,XN(7)],孕28周时终止妊娠。母亲第3胎妊娠早期入院检查,为进一步明确先证者病因,采用冻存的先证者DNA进行全外显子分析,除PAH复合杂合变异外,检出GABRA2基因新发致病变异c.875C>G,证实先证者共患发育性癫痫性脑病78型。第3胎胎龄18周时羊水细胞基因分析发现PAH基因存在与先证者相同的复合杂合变异,GABRA2基因未检出c.875C>G变异。母亲选择继续妊娠,第3胎为男婴,足月顺产出生,于日龄3 d时确诊PKU,遂开始规范低苯丙氨酸饮食与监测,血苯丙氨酸控制在正常范围,目前3岁,智力、运动及体格发育良好。结论PKU为严重的遗传代谢病,经规范治疗后绝大多数患者预后良好。Objective Through the diagnosis and intervention of different genetic defects in three siblings,the strategies of genetic diagnosis and prenatal diagnosis were discussed.Methods The genetic diagnosis was conducted via a biochemical assay,gene study and chromosome analysis.The prenatal diagnosis of the third fetus was carried out by amniocyte gene analysis.Results The proband,male,presented delayed development at the age of 2 months.His blood phenylalanine was markedly elevated(>1200μmol/L).Complex heterozygously reported pathogenic variations(c.728G>A and c.1068C>A)in PAH gene were detected,which confirmed the diagnosis of classic phenylketonuria.After a treatment by the standardized phenylalanine-restricted diet,his blood phenylalanine was well maintained.When he was 3 months old,he developed intractable epilepsy,severe mental impairment and died at the age of 14 years.During the mother's second pregnancy,the fetus was found to have omphalocele and chromosomal disorders[45,XN,-21(3)/46,XN(7)]via amniocyte analysis.The pregnancy was terminated at 28 weeks.The mother visited us for the prenatal diagnosis of her third fetus.In order to further clarify the etiology of the proband,whole exon sequencing was performed using frozen proband DNA.In addition to c.728G>A and c.1068C>A on the PAH gene,a novel pathogenic variant c.875C>G on GABRA2 gene was identified,which confirmed that the proband had PKU complicated with developmental and epileptic encephalopathy-78.At the 18th week of the third pregnancy,amniocyte gene analysis was performed.The PAH gene had the same compound heterozygous variation as in the proband,but c.875C>G on GABRA2 gene was not detected.The mother chose to continue the pregnancy.The third child,a boy,was delivered naturally at full term.Phenylketonuria was diagnosed at 3 days of age.Standardized low phenylalanine diet and monitoring were initialed.His blood phenylalanine was maintained at optimal levels.He was now 3 years old with normal mental and physical development.Conclusion Phenylketonuria i

关 键 词：遗传代谢病 苯丙酮尿症 苯丙氨酸 难治性癫痫 基因 产前诊断 

分 类 号：R715.5[医药卫生—妇产科学]