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目的明确1例肝肾发育异常患儿的遗传学病因。方法收集该患儿的家族史及临床资料,抽取患儿及其父母外周静脉血2 mL,对患儿基因组DNA进行新一代测序分析,并对疑似致病性突变位点进行Sanger测序验证及生物信息学预测。结果该患儿系第三胎第一产,前2胎均在围产期死亡,B超示多囊肾表现。该患儿为男性,4月大,腹部膨隆可触及质硬包块,腹部超声提示多囊肾并肝纤维化,新一代测序显示患儿PKHD1基因第30外显子c.3500T>C(p.L1167P)杂合突变,遗传自母亲;另外患儿PKHD1基因第58外显子c.9235_9236del GCins AA(p.A3079K)杂合突变,来自父亲;父母表型均正常,这2个突变均为新发现的突变。结论该患儿是由PKHD1基因的复合杂合突变导致的常染色体隐性遗传多囊肾病(ARPKD),结合家族史推断,该家系前2胎可能同样患有ARPKD。新一代测序可对该类疾病明确诊断,并有助于遗传咨询,以避免该类悲剧的再次发生。
Objective To clarify the genetics of a child with abnormal liver and kidney development. Methods The family history and clinical data of the children were collected. 2 mL peripheral venous blood samples were collected from children and their parents, and a new generation of genomic DNA was sequenced. Sanger sequencing and biological Informatics forecast. Results The third trimester of the child was the first birth, the first two tires were perinatal death, B ultrasound showed polycystic kidney disease. The child was male, with a large abdomen in April and bulging abdomen to reach hard mass. Abdominal ultrasonography showed polycystic kidney disease and liver fibrosis. A new generation of sequencing showed that c.30500T> C (p .L1167P) heterozygous mutation, inherited from the mother; other children PKHD1 gene exon 58 c.9235_9236del GCins AA (p.A3079K) heterozygous mutation, from the father; both parents were normal phenotype, these two mutations were Newly discovered mutations. Conclusions This patient is autosomal recessive polycystic kidney disease (ARPKD) caused by compound heterozygous mutation of PKHD1 gene. According to family history, the first two fetuses may also have ARPKD. Next-generation sequencing can provide a definitive diagnosis of such diseases and help in genetic counseling to avoid the recurrence of such tragedies.