Case Report: A Novel Missense Mutation c.517G>C in the Gene Associated With Mild Orotic Aciduria.

Background: Hereditary orotic aciduria (HOA) is a rare genetic disorder of pyrimidine metabolism caused by variations in the uridine monophosphate synthetase () gene and inheritance are autosomal recessive. Heterozygous mutations can also lead to orotic aciduria without clinical consequence.

Methods: We conducted molecular genetic analyses on proband using whole-exome sequencing (WES) and on 12 family members using Sanger sequencing for mutation. We analyzed the urine metabolites of family members carrying heterozygous variants with standard gas chromatography-mass spectrometry (GC-MS).

Results: We identified a novel mutation (c.517G>C) in a Chinese-origin of orotic aciduria pedigree. The proband presented with epilepsy and intellectual disability (ID). Other mutation carriers in our pedigree presented with mild orotic aciduria without relevant medical complaints except for the proband.

Conclusion: Our study further expanded the genotype of orotic aciduria and highlighted the probability of misdiagnosis in clinical practice.