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

Abstract

Objective To investigate the genetic causes of a patient with liver and kidney dysplasia. 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.L1167P) 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. Key words: Autosomal recessive polycystic kidney disease (ARPKD); PKHD1; Next generation sequencing