Possible PKHD1 Hot-spot Mutations Related to Early Kidney Function Failure or Hepatofibrosis in Chinese Children with ARPKD: A Retrospective Single Center Cohort Study and Literature Review

• Published in: Current medical science Vol. 40; no. 5; pp. 835 - 844
• Main Authors: Qiu, Li-ru, Xu, Rong-rong, Tang, Jin-hui, Zhou, Jian-hua
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.10.2020; Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
• Subjects: Medicine; Medicine & Public Health; autosomal recessive polycystic kidney disease; mutations; genotypic characteristics; Chinese children; clinical phenotype; PKHD1 mutations
• ISSN: 2096-5230; 1672-0733; 2523-899X
• DOI: 10.1007/s11596-020-2268-z

Summary PKHD1 mutations are generally considered to cause autosomal recessive polycystic kidney disease (ARPKD). ARPKD is a rare disorder and one of the most severe conditions leading to end-stage renal disease in childhood. With the biallelic deletion mutation, patients have difficulty in surviving the perinatal period, resulting in perinatal or neonatal death. This study retrospectively analyzed patient characteristics, imaging characteristics, laboratory examinations and family surveys from 7 Chinese children with different PKHD1 gene mutations diagnosed by high-throughput sequencing from January 2014 to February 2018. Of the 7 children, there were 3 males and 4 females. Eight missense mutations, two frameshift mutations, two deletion mutations, and two intronic slicing mutations were identified. Six of the mutations have not previously been identified. In the literature search, we identified a total of 29 Chinese children with PKHD1 mutations. The missense mutation c.2507T>C in exon 24 was found in one patient in our study, and five patients with liver fibrosis but normal renal function were reported in the literature. The missense mutation c.5935G>A in exon 37 was found in two patients in our study and three cases in the literature. Four patients had renal failure at an age as young as 1 year of those five patients with the missense mutation c.5935G>A in exon 37. It was concluded that: (1) Kidney length more than 2–3 SDs above the mean and early-onset hypertension might be associated with PKHD1 -associated ARPKD; (2) The more enlarged the kidney size is, the lower the renal function is likely to be; (3) c.5935G>A may be a hot spot that leads to early renal failure in Chinese children with PKHD1 mutations; (4) c.2507T>C may be a hot-spot mutation associated with hepatic lesions in Chinese children with PKHD1 .