新一代测序技术确诊1例遗传多囊肾病家系

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.3500TC(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。

Next generation sequencing for diagnosis of a patient with autosomal recessive polycystic kidney disease

Objective To investigate the genetic causes of a patient with liver and kidneydysplasia Methods Clinical data of the patient and the family history were collected.The DNA of the patient and his parents was extracted and sequenced by next generation sequencing.The results were predicted and validated using Sanger sequencing.Results The patient was the first child and the third fetus in the family.The previous two fetuses were dead in the prenatal period with ultrasound showing polycystic kidney.The patient,a 4-month-old boy,had an abdominal distension with a touchable hard lump in his abdomen.Abdominal ultrasound revealed that he had polycystic kidney and fibrotic liver.Sequencing result showed a mutation of c.3500T＞C (p.L 1167P) in PKHD1 exon 30 inherited from his mother and a mutation of c.9235_9236delGCinsAA (p.A3079K) in PKHD1 exon 58 inherited from his father.Both mutations were novel mutations.Conclusion The patient was diagnosed as an autosomal recessive polycystic kidney disease (ARPKD) caused by PKHD1 compound heterozygous mutations.It is inferred that the previous two dead fetuses might suffer from ARPKD like this patient,thus the next generation sequencing contributes to diagnose such diseases and facilitates genetic counseling in order to avoid the family tragedy.