Mutation Hot Spot Region in the HOGA1 Gene Associated with Primary Hyperoxaluria Type 3 in the Chinese Population

Background: Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder that affects glyoxylate metabolism. PH3 is caused by defects in 4-hydroxy-2-oxoglutarate aldolase, which is encoded by the HOGA1 gene. However, only 3 cases of PH3 have been described in Asians until today. This study aimed to determine the clinical and mutation spectra of patients from mainland China with PH3. Methods: We applied targeted next-generation sequencing to four non-consanguineous, unrelated Chinese families with PH3 to identify the genes hosting disease-causing mutations. This approach was confirmed by Sanger sequencing. Results: Five patients (2 boys and 3 girls) from four unrelated Chinese families were admitted because of kidney stones. Five HOGA1 gene sequence mutations were detected, including two novel mutations, c.811C>T (p.R271C) and c.812G>A (p.R271H). These compound heterozygous mutations were detected in a female PH3 patient (patient 4). Other patients included 2 boys who had heterozygous c.834_834+1GG>TT and c.834G>A (p.A278A) mutations (patients 1 and 2), a girl with homozygous c.834G>A (p.A278A) mutation (patient 3), and a girl with heterozygous c.834_834+1GG>TT and c.346C>T (p.Q116X) mutations (patient 5). The mutations in the c.834_834+1 region, including c.834G>A, c.834+1G>T, and c.834_834+1GG>TT, account for 5/8 of alleles in our study and 3/4 of alleles reported among Chinese patients. All patients in this study received hyperhydration and urine alkalinization treatment. Conclusion: Five PH3 cases were reported. Potential mutation hot spot region (c.834_834+1) in the Chinese population and two novel mutations were found.