新疆四个苯丙酮尿症家系的基因诊断

Gene diagnosis of phenylketonuria of 4 families in Xinjiang

目的 :研究新疆苯丙酮尿症 (PKU )家系苯丙氨酸羟化酶 (PAH)基因突变位点及其遗传标记 ,探索适合新疆各民族 PKU基因诊断和产前基因诊断途径。方法 :联合采用 PCR- STR、ASPCR和 PCR- SSCP 3种基因诊断方法进行分析。结果 :(1) PCR- STR连锁分析表明 :除家系 4母亲为 STR纯合型外 ,其余家系双亲皆为杂合子。对家系 1(维吾尔族 ) 1例风险胎儿 (妊娠 6周 ,流产 )进行产前基因诊断和 1例新生儿 (出生 1d)进行症前基因诊断 ,均为携带者 ,并经出生后证实。 (2 )采用 ASPCR法在家系 1、2和 3均未检出 R2 43Q和 R413P两种常见突变。 (3)应用 PCR- SSCP分析发现 ,家系 2 (回族 )患儿为外显子 7突变纯合子 ,家系 4(汉族 )患儿为外显子 7和外显子 11突变复合体 ,其外显子 11突变位于第 399位点 (GTA→ GTT) ,可能为一致病突变。 结论 :上述 3种基因诊断方法联合使用简便、快捷 ,适合新疆地区的基因诊断和产前基因诊断。

Objective: To evaluate a fittable PKU gene diagnosis and prenatal gene diagnosis in Xinjiang. Methods: Three gene diagnosis methods, polymerase chain reaction short tandem repeats (PCR STR)、 allele specific PCR(ASPCR) and PCR single strand conformation polymorphism(PCR SSCP)were used to analyze phenylalanine hydroxylase (PAH)gene of 4 familes affected with phenylketonuria(PKU) . Results: With linkage analysis by STR, accurate gene diagnosis can be made in 3 familes, except in family 4 only 50% exclusive diagnosis can be made due to the mother is homozygote for STR. One prenatal gene diagnosis and one postnatal gene diagnosis on a new born were performed in family 1,a Uygur family,both of the fetus and new born are heterozygotes . The two most frequent known gene mutations,e.g., R243Q and R413P weren't detected in family 1,2 and 4 by ASPCR. No mutation was detected in exons 4～7 and 10～12 in family 1 by PCR SSCP. It was found that the proband in family 2 (Hui) is homozygote for exon 7 mutation. The proband in family 4 is compound for mutation in exon 7 and codon 399 (GTA GTT) in exon 11.Conclusion: Accurategenediagnosiscanbeachievedinthesefamileswiththecombinedmethods.