Presentation Authors: wenying wang*, Jun Li, beijing, China, People's Republic of
Introduction: Primary hyperoxaluria type 3(PH3) is an autosomal recessive metabolic disorder caused by inherited mutations in the HOGA1 gene. Nearly thirty HOGA1 mutations have been reported in PH3 with c.700+5G>T accounting for about 50% of the total alleles in the literatures. Only one case with PH3 was reported in Asian. The aim of our study was to analyze and characterize the mutational spectrum of PH3 in Chinese pediatric patients with kidney stones.
Methods: Ninety-five pediatric patients with early-onset nephrolithiasis were suspected of having PH. DNA was extracted from patientâ€™s white blood cell. The whole exome sequencing was performed. We searched for AGXT, GRHPR and HOGA1 gene mutations in the patients and his parents. All coding regions, including exon, intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis.
Results: PH1, PH2 and PH3 were found in 7, 4 and 10 pediatric patients respectively. Among of PH3 patients, 8 were boys and 2 were girls, the mean age was 35 months.Three mutations not previously described in the literature about HOGA1 were identified (compound heterozygous or homozygous). The most commonly mutation was seen in 6 patients, which was a guanine to adenine substitution of the last nucleotide of exon (c.834G>A). One patient with PH3 was also found to have the mutation of ADCY10 gene at the same time. In addition, three SNPs were found in these family (c.812G>A, c.952C>T and c.811C>T).
Conclusions: This is the largest cases reporting PH3 mutations in Asian families. Three novel HOGA1 mutations were found in associated with PH3, and c.834G>A was the most commonly seen mutation of PH3 in Chinese pediatric patients with kidney stones. Future investigation in Chinese pediatric populations, especially cases with PH3 genotype and phenotype, are highly needed.