Type I hyperprolinemia: Genotype/phenotype correlations

Audrey Guilmatre, Solenn Legallic, Gary Steel, Alecia Willis, Gabriella Di Rosa, Alice Goldenberg, Valérie Drouin-Garraud, Agnès Guet, Cyril Mignot, Vincent Des Portes, Vassili Valayannopoulos, Lionel Van Maldergem, Jodi D. Hoffman, Claudia Izzi, Caroline Espil-Taris, Simona Orcesi, Luisa Bonafé, Eric Le Galloudec, Hélène Maurey, Christine IoosAlexandra Afenjar, Patricia Blanchet, Bernard Echenne, Agathe Roubertie, Thierry Frebourg, David Valle, Dominique Campion

Research output: Contribution to journalArticlepeer-review


Type I hyperprolinemia (HPI) is an autosomal recessive disorder associated with cognitive and psychiatric troubles, caused by alterations of the Proline Dehydrogenase gene (PRODH) at 22q11. HPI results from PRODH deletion and/or missense mutations reducing proline oxidase (POX) activity. The goals of this study were first to measure in controls the frequency of PRODH variations described in HPI patients, second to assess the functional effect of PRODH mutations on POX activity, and finally to establish genotype/enzymatic activity correlations in a new series of HPI patients. Eight of 14 variants occurred at polymorphic frequency in 114 controls. POX activity was determined for six novel mutations and two haplotypes. The c.1331G>A, p.G444D allele has a drastic effect, whereas the c.23C>T, p.P8L allele and the c.[56C>A; 172G>A], p.[Q19P; A58T] haplotype result in a moderate decrease in activity. Among the 19 HPI patients, 10 had a predicted residual activity A, p.T275N allele, which has no detrimental effect on activity but whose frequency in controls is only 3%. Our results suggest that PRODH mutations lead to a decreased POX activity or affect other biological parameters causing hyperprolinemia.

Original languageEnglish
Pages (from-to)961-965
Number of pages5
JournalHuman Mutation
Issue number8
Publication statusPublished - Aug 2010


  • 22q11
  • POX enzymatic activity
  • Type I hyperprolinemia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Type I hyperprolinemia: Genotype/phenotype correlations'. Together they form a unique fingerprint.

Cite this