Identification of 8 novel gene variants in primary hyperoxaluria in 21 Chinese children with urinary stones

Purpose We analyzed primary hyperoxaluria (PH) genotype and phenotype in Chinese children. Vitamin B 6 response in the patients with genetically confirmed PH1 was also studied. Methods We, respectively, analyzed 80 children with urinary stones. Sixty-four children were diagnosed with hyperoxaluria. Twenty-one children consented to genetic evaluation (targeted gene panel-based and whole-exome sequencing), and DNA was obtained from the children and both the parents. Results PH accounted for 57.1% (12/21) of hyperoxaluria cases. We reported 12 PH cases, including 5 PH1, 1 PH2, and 6 PH3 cases; 2 novel mutations in AGXT and GRHPR each and 4 HOGA1 mutations were identified. The mutations in AGXT and GRHPR were c0.1161C>A and c0.551C>A, and c0.370C>T and c0.864_865delTG, respectively. Four HOGA1 mutations, c0.290G>A, c0.110G>A, c0.554C>T and c0.834_834 + 1delinsTT, were not reported previously. The average urine Ox 24 level in the PH patients was 0.91 mmol/1.73 m 2 . Moreover, the average urine Ox 24 level in the PH1 patients (1.07 mmol/1.73 m 2 ) was higher than that in the PH2 and PH3 patients (0.73 mmol/1.73 m 2 and 0.71 mmol/1.73 m 2 , respectively). The eGFR of the PH1 patients (76.86 mL/min) was lower than that of the PH2 and PH3 patients (132 mL/min and 136 mL/min, respectively). Conclusions PH incidence was higher than the reported PH incidence in children with urinary stones. Hence, we suggested that genetic examination was necessary for all the children with hyperoxaluria. These novel mutations broaden the range of known gene mutations in PH.