婴儿型多囊肾家系PKHD1基因的突变分析

Mutational analysis in PKHD1 gene from a family of infantile polycystic kidney

目的对1个婴儿型多囊肾家系的致病基因PKHD1进行突变分析。方法先证者母亲怀孕两次,胎儿均在围产期死亡,且两次胎儿彩超结果相似,符合多囊肾改变。提取先证者父母及其他成员外周血基因组DNA,PCR扩增PKHD1基因编码区并进行序列测定;找到突变后,对相应PCR产物进行酶切鉴定或变性高效液相色谱分析,以证实突变。结果先证者家系成员序列分析表明,其父和祖母PKHD1基因第59外显子存在杂合突变(c.9901G>T),其母和外祖母PKHD1基因第53外显子存在杂合的缺失突变(c.8317delG)。两个突变均导致mRNA提前出现终止密码子。结论发现两个新的PKHD1基因突变;若胎儿同时遗传了这两个突变,将导致婴儿型多囊肾的发生。

Objective To investigate PKHD1 gene mutation in a family of autosomal recessive polycystic kidney disease. Methods The mother of proband had conceived two babies, but both of them had died during perinatal period. The results of ultrasound checking for two fetuses were similar and coincidental with the disease of polycystic kidney. The coding region ofPKHD1 gene from the genomic DNA of peripheral blood cells from the proband＇s parents and other family members was PCR amplified and sequenced. The products of PCR were digested by restriction enzymes or analyzed through DHPLC to confirm the mutations. Results Sequence analysis showed that there were a heterozygous mutation（c.9901G〉T） in exon 59 ofPKHD1 gene from the father and the paternal grandmother, and a heterozygous deletion mutation（c.8317delG） in exon 53 of PKHD1 gene from the mother and the maternal grandmother. Both mutations were novel, leading to premature termination codons. Conclusion Two novel mutations in PKHD1 were found. If they were transmitted to the offsprings, infantile polycystic kidney would occur.