Document Detail

Mutations in the Delta1-pyrroline 5-carboxylate dehydrogenase gene cause type II hyperprolinemia.
MedLine Citation:
PMID:  9700195     Owner:  NLM     Status:  MEDLINE    
We surveyed Delta1-pyrroline 5-carboxylate dehydrogenase genes from four patients with hyperprolinemia type II using RT-PCR amplification, genomic PCR amplification and direct sequencing. We found four mutant alleles, two with frameshift mutations [A7fs(-1) and G521fs(+1)] and two with missense mutations (S352L and P16L). To test the functional consequences of three of these, we expressed them in a P5CDh-deficient strain of Saccharomyces cerevisiae . In contrast to wild-type human P5CDh, yeast expressing S352L and G521fs(+1) failed to grow on proline and had no detectable P5CDh activity. The P16L allele, however, produced fully functional P5CDh and subsequent analysis suggests that it is polymorphic in the relevant (Spanish) population. Interestingly, the G521fs(+1) allele segregates in the large Irish Traveller pedigree used to define the HPII phenotype. To our knowledge, this is the first description of the molecular basis for this inborn error.
M T Geraghty; D Vaughn; A J Nicholson; W W Lin; G Jimenez-Sanchez; C Obie; M P Flynn; D Valle; C A Hu
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human molecular genetics     Volume:  7     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-10-16     Completed Date:  1998-10-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1411-5     Citation Subset:  IM    
Institute for Genetic Medicine, Department of Pediatrics, Predoctoral Training Program in Human Genetics and Molecular Biology and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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MeSH Terms
1-Pyrroline-5-Carboxylate Dehydrogenase
Amino Acid Metabolism, Inborn Errors / classification,  enzymology*,  genetics*
Amino Acid Sequence
Base Sequence
Cell Line
DNA Primers / genetics
DNA, Complementary / genetics
Frameshift Mutation
Gene Expression
Oxidoreductases Acting on CH-NH Group Donors / genetics*
Point Mutation
Polymerase Chain Reaction
Proline / metabolism*
Saccharomyces cerevisiae / genetics,  growth & development,  metabolism
Grant Support
Reg. No./Substance:
0/DNA Primers; 0/DNA, Complementary; 147-85-3/Proline; EC 1.5.-/Oxidoreductases Acting on CH-NH Group Donors; EC Dehydrogenase; EC protein, human

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