1例常染色体隐性遗传多囊肾的PKHD1基因分析

PKHD1 gene analysis in a newborn with autosomal recessive polycystic kidney disease

目的 对1例患常染色体隐性遗传多囊肾疾病（ARPKD）的新生儿进行家族史、临床、病理调查,并对致病基因PKHD1进行突变鉴定,探讨该病的临床特点和分子发病机制.方法 根据患儿产前超声、临床表现、死亡后病理检查及家族史进行临床诊断,应用PCR扩增、DNA直接测序技术对患儿及其父母进行PKHD1基因突变分析.结果 患儿PKHD1基因第58号外显子发生了无义突变c.9319C〉T,从而使PKHD1蛋白多肽链的合成提前终止.结论 ARPKD可在胎儿期及生后早期导致不良的结局,临床医生应提高对该病的认识,PKHD1基因突变是ARPKD的遗传基础,进行PKHD1基因突变分析有助于产前基因诊断技术的开展.

Objective To investigate the clinical characteristics and molecular pathogenesis of autosomal recessive polycystic kidney disease （ARPKD） by studying the family history, clinical and pathological manifestation of one neonate and identifying PKHD1 nmtation. Methods Diagnosis of ARPKD was conducted according to antenatal ultrasonic examination, typical clinical manifestations, postmortem pathological examination and family history. PCR-DNA direct sequencing method was used to screen the exons of PKHD1 gene for mutation analysis both for neonate and parents. Results The PKHD1 gene sequencing revealed a nonsense mutation in exon 58 （ c. 9319C 〉 T）, which resulted in termination of PKHDI polypeptide chain ahead of schedule. Conclusion ARPKD can induce devastating results in foetal period and early postnatal period, so clinicians should improve cognition on the disease. PKHD1 gene mutation is the genetic basis of ARPKD, and PKHD1 gene mutation analysis is beneficial to carry out antenatal gene diagnosis technology.