Human Molecular Genetics, Vol 7, 1411-1415, Copyright © 1998 by Oxford University Press
MT Geraghty, D Vaughn, AJ Nicholson, WW Lin, G Jimenez-Sanchez, C Obie, MP Flynn, D Valle and CA Hu
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.
ARTICLES
Mutations in the Delta1-pyrroline 5-carboxylate dehydrogenase gene cause type II hyperprolinemia
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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