Phenotype analysis of 9 cases with mutations in PKHD1 gene

Abstract

Objective To summarize the clinical features of 9 cases with mutations in PKHD1 gene for a better understanding of its phenotype. Methods Clinical data of nine cases with mutations in PKHD1 gene were summarized from January 2011 to December 2016 in our center, including clinical manifestations, laboratory findings, imaging data and family investigation. Next generation sequencing was used to screen 4000 genes in case 1 to 4 and whole exons in case 5 to 9. Significant variants detected by next generation sequencing were confirmed by conventional Sanger sequencing. Segregation analysis was performed using parental DNA samples. Relevant literature was reviewed. Results Among these 9 cases, 5 are male, 4 are female. The average age of onset was 2.6 years old (ranging from 0.5-5.2 years). Renal ultrasound revealed that all 9 cases had cysts in bilateral kidney, 7 cases with enlarged kidney, 1 case with normal size kidney, 1 case with normal size kidney, and 1 case with bilateral renal atrophy. Two cases with renal artery stenosis, 1 case with focal narrowing in left main branch and 1 case with vesico-ureteral reflux were found. Among the 9 cases, 3 cases had homozygous mutations, and 6 cases had compound heterozygous mutations, including 1 nonsense mutation, 1 frameshift mutation and 15 missense mutations. There were 2 cases with 3 heterozygous mutations, 2 c.5935C>T mutations and 2 cases with C. 5869G>A mutations. A total of 10 new mutations were identified. Conclusion Patients with mutations in the PKHD1 gene had normal size kidney, or even atrophic kidney. Renal artery stenosis, vesicoureteral reflux and bronchial stenosis were all first reported in patients with mutations in PKHD1 gene. The novel mutations, c.274C>T, c.9059T>C, c.8996delG, c.281C>T, c.10424T>A, c.7092T>G, c.4949T>C, c.5869G>A, c.6197A>G and c.1877A>G further expanded the mutation spectrum of PKHD1 gene. Key words: Phenotype; Polycystic kidney, autosomal recessive; Renal artery obstruction; PKHD1 gene; Atrophic kidney