苯丙酮尿症一家系的基因诊断及产前诊断研究  

Genetic analysis and prenatal diagnosis of a phenylketonuria pedigree

作　　者：朱海燕[1] 季春燕[1] 张海荣[1] Zhu Haiyan;Ji Chunyan;Zhang Hairong(Prenatal Diagnosis Center, Department of the Gynecology and Obstetrics, Navy General Hospital, Beifing 100048, China)

机构地区：[1]中国人民解放军海军总医院妇产科产前诊断中心,北京100048

出　　处：《中华检验医学杂志》2018年第4期312-315,共4页Chinese Journal of Laboratory Medicine

摘　　要：目的对有苯丙酮尿症（PKU）家族史的孕妇（先证者姨妈）提供遗传咨询，为家系内的先证者进行基因诊断，明确致病突变及家系成员基因型，为孕妇提供产前诊断。方法临床实验诊断研究，对2016年10月在海军总医院就诊、进行遗传咨询的孕妇及家系成员进行基因诊断。应用Sanger测序方法，对患儿的苯丙氨酸羟化酶基因（PAH）进行序列分析，针对检测到的突变对家庭成员进行检测，明确致病突变。患儿母亲的妹妹（姨妈）妊娠，对其胎儿进行相应位点的突变分析，同时采用片段长度多态性方法，对家系成员PAH基因3号内含子的短串联重复（STR）位点进行单体型分析。结果序列分析显示患儿PAH基因IVS4－1G〉A/c.770G〉T复合杂合突变，分别来自其母亲和父亲；患儿姨妈同为IVS4－1G〉A杂合突变携带者，其丈夫为c.827T〉A杂合突变携带者；为胎儿进行了产前基因诊断显示仅遗传了其父亲的c.827T〉A杂合突变，且STR单体型与先证者不同。结论对于常染色体隐性遗传病，同一家系中的携带者组成的不同家庭，在遗传咨询中，均需要明确配偶是否为致病基因携带者，充分评估胎儿发病风险。Objective To provide genetic counselling for a pregnant with phenylketonuria （PKU） family history. To provide prenatal diagnosis for the pregnant of the pedigree, followed by identifying of the pathogenic mutation of the proband and the genotype of the other family members. Methods Sanger sequencing was performed to detect the phenylalanine hydroxylase （PAH） gene pathogenic mutation of the patient. Both sequencing and haplotype of the short tandem repeats （STR） site in intron 3 were analyzed for the fetus, whose mother was the aunt of the patient. Results Compound heterozygote mutation of PAH gene, IVS4-1G 〉 A/c. 770G 〉 T was identified for the proband, which inherited from his father and mother respectively. The aunt of the patient was a carrier of the IVS4-1G 〉 A heterozygote mutation, whose husband was identified e. 827T 〉 A heterozygote mutation. Prenatal diagnosis disclosed that the fetus inherited the paternal c. 827T 〉 A mutation, and the haplotype of the PAH gene was different from the patient. Conclusion According to the counselling of autosomal recessive disorder, for the partner of a carrier, it is suggested that mutation detection should be performed to exclude the possibility of being a carrier too, and then the risk of the offspring can be evaluated precisely.

关 键 词：苯丙酮尿症 PAH基因 基因突变 产前诊断 

分 类 号：R440[医药卫生—诊断学] R714.5[医药卫生—临床医学]