A novel splicing mutation in the PKD1 gene causes autosomal dominant polycystic kidney disease in a Chinese family
作者单位：Center for Reproductive Medicine
会议名称：《第一届中国临床分子诊断大会》
会议日期：2018年
学科分类：100208[医学-临床检验诊断学] 1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学]
关 键 词：Autosomal Dominant Polycystic Kidney Disease PKD1 gene Novel splice mutation Frameshift mutation
摘 要：Background Autosomal dominant polycystic kidney disease（ADPKD） is the most common monogenic renal disorder in humans, affecting 1 in 400 to 1000 individuals. Mutations PKD1（which accounts for 85% of ADPKD and produces polycystin-1） and PKD2（produces polycystin-2） are responsible for this disease. These two polycystins are critical for maintaining normal renal tubular structures during kidney development. Case presentation We performed genetic analysis on a family with ADPKD. DNA samples extracted from ADPKD patient blood were subject to targeted Next generation sequencing for human a panel of renal disease-related genes. A splicing mutation, c.2854-3 CG（also known as IVS11-3 CG）, in the PKD1 gene was found in the 3 patients from the family, but was not found in four unaffected relatives and 100 normal control samples. Reverse transcription-PCR（RT-PCR） was performed to analyse the relative m RNA expression in the patient samples. mRNA sequencing showed that 29 bases inserted into the 3’-end of exon 11 in the PKD1 gene lead to a frameshift mutation. Conclusions The PKD1 c.2854-3 CG mutation leads to a frameshift mutation during translation of the polycystin-1 protein, which eventually led to ADPKD in the Chinese family.