TY - JOUR
T1 - Type I hyperprolinemia
T2 - Genotype/phenotype correlations
AU - Guilmatre, Audrey
AU - Legallic, Solenn
AU - Steel, Gary
AU - Willis, Alecia
AU - Di Rosa, Gabriella
AU - Goldenberg, Alice
AU - Drouin-Garraud, Valérie
AU - Guet, Agnès
AU - Mignot, Cyril
AU - Des Portes, Vincent
AU - Valayannopoulos, Vassili
AU - Van Maldergem, Lionel
AU - Hoffman, Jodi D.
AU - Izzi, Claudia
AU - Espil-Taris, Caroline
AU - Orcesi, Simona
AU - Bonafé, Luisa
AU - Le Galloudec, Eric
AU - Maurey, Hélène
AU - Ioos, Christine
AU - Afenjar, Alexandra
AU - Blanchet, Patricia
AU - Echenne, Bernard
AU - Roubertie, Agathe
AU - Frebourg, Thierry
AU - Valle, David
AU - Campion, Dominique
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - 22q11
KW - POX enzymatic activity
KW - PRODH
KW - Type I hyperprolinemia
UR - http://www.scopus.com/inward/record.url?scp=77955085263&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955085263&partnerID=8YFLogxK
U2 - 10.1002/humu.21296
DO - 10.1002/humu.21296
M3 - Article
C2 - 20524212
AN - SCOPUS:77955085263
VL - 31
SP - 961
EP - 965
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 8
ER -