A novel stop-gain mutation in DPYS gene causing Dihidropyrimidinase deficiency, a case report

Malihe Mirzaei, Arghavan Kavosi, Mahboobeh Sharifzadeh, Ghazale Mahjoub, Mohammad Ali Faghihi, Parham Habibzadeh, Majid Yavarian

Research output: Contribution to journalArticlepeer-review


Background: Dihidropyrimidinase (DHP) deficiency is an inherited inborn error of pyrimidine metabolism with a variable clinical presentation and even asymptomatic subjects. Dihydropyrimidinase is encoded by the DPYS gene, thus pathogenic mutations in this gene can cause DHP deficiency. To date, several variations in the DPYS gene have been reported but only 23 of them have been confirmed to be pathogenic. Therefore, the biochemical, clinical and genetic aspects of this disease are still unclear. Case presentation: Here, we report a 22-year-old woman with DHP deficiency. To identify the genetic cause of DHP deficiency in this patient, Whole Exome Sequencing (WES) was performed, which revealed a novel homozygote stop gain mutation (NM_001385: Exon 9, c.1501 A > T, p.K501X) in the DPYS gene. Sanger sequencing was carried out on proband and other family members in order to confirm the identified mutation. According to the homozygote genotype of the patient and heterozygote genotype of her parents, the autosomal recessive pattern of inheritance was confirmed. In addition, bioinformatics analysis of the identified variant using Mutation Taster and T-Coffee Multiple Sequence Alignment showed the pathogenicity of mutation. Moreover, mRNA expression level of DPYS gene in the proband's liver biopsy showed about 6-fold reduction compared to control, which strongly suggested the pathogenicity of the identified mutation. Conclusions: This study identified a novel pathogenic stop gain mutation in DPYS gene in a DHP deficient patient. Our findings can improve the knowledge about the genetic basis of the disease and also provide information for accurate genetic counseling for the families at risk of these types of disorders.

Original languageEnglish (US)
Article number138
JournalBMC medical genetics
Issue number1
StatePublished - Jun 29 2020


  • Case report
  • DPYS
  • Dihidropyrimidnase deficiency (DHP deficiency)
  • Novel stop gain mutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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