三种单基因遗传病的产前分子诊断 [中文引用][英文引用]

目的 探讨脊髓性肌萎缩症（SMA）、苯丙酮尿症（PKU）和先天性软骨发育不全（ACH）产前基因诊断的高效的临床检测方法。方法 根据不同单基因病的基因突变类型，本研究应用DHPLC技术对1例SMA阳性家族史的胎儿绒毛样本进行SMN1基因7号外显子缺失检测，选择正常人及SMA患者作对照。通过直接测序法分别对PKU家系和ACH家系的患者，表型正常的个体及其胎儿进行PAH致病基因和FGFR3基因第10外显子进行检测。结果 SMA阳性家系中，胎儿未检测到SMN1基因7号外显子的纯合缺失，建议继续妊娠，结果顺利产出1名正常儿。PKU阳性家系通过检测发现患者在PAH基因上确实存在无义突变，c.781C>T（p.Arg261Ter）和错义突变c.842C>T（p.Pro281Leu），均为杂合子。但是胎儿与患者母亲的突变类型一致，为携带者，不发病，建议继续妊娠。软骨发育不全患者送检标本FGFR3基因外显子10发现1处序列异常，为c.1138G>A，导致编码氨基酸改变Gly380Arg，但其胎儿羊水标本检测FGFR3基因外显子10未发现序列异常。结论 根据单基因病不同的基因突变类型，选择合适的方法可快速、准确地实现单基因病产前基因的诊断，尽早避免单基因病患儿的出生。

Objective To investigate methods for prenatal diagnosis of spinal muscular atrophy (SMA), PKU and achondroplasia (ACH). Method Different test methods are applied based on different mutational pattern. The chorionic villus of 1 fetus with SMA positive family history was collected. The exon 7 of telomeric survial motor neuron (SMN1) gene was detected by DHPLC. Normal member and SMA patient were selected as controls. The hot mutation in exon 10 of FGFR3 gene and PAH gene were detected by DNA sequencing in patients, normal phenotype individuals and pregnancy fetus. Results Homozygous deletion of the SMN1 exon7 wasn’t detected in pregnancy fetus. The pedigree diagnosed as negative continued to pregnancy, and gave birth to a normal baby. c.781C>T (p.Arg261Ter) and c.842C>T (p.Pro281Leu) mutations of PAH gene were detected in patient with PKU positive family history. Fortunately,Sequencing analysis revealed the fetus shows the mutation of PAH gene as same as his mother c.842C>T (p.Pro281Leu). The pedigree diagnosed as carrier continued to pregnancy. The mother of the fetus diagnosed as achondroplasia had G1138A mutation, but the fetus had normal nucleotide at nucleotide 1138 in exton 10of FGFR3, therefore were excluded from achondroplasia. Conclusions The application of different test methods is efficient and practical ways in different monogenic disease.