Angel L. Pey and Lourdes R. Desviat contributed equally to this work.
Phenylketonuria: Genotype–phenotype correlations based on expression analysis of structural and functional mutations in PAH†
Version of Record online: 19 MAR 2003
Copyright © 2003 Wiley-Liss, Inc.
Volume 21, Issue 4, pages 370–378, April 2003
How to Cite
Pey, A. L., Desviat, L. R., Gámez, A., Ugarte, M. and Pérez, B. (2003), Phenylketonuria: Genotype–phenotype correlations based on expression analysis of structural and functional mutations in PAH. Hum. Mutat., 21: 370–378. doi: 10.1002/humu.10198
For the PKU special issue
- Issue online: 19 MAR 2003
- Version of Record online: 19 MAR 2003
- ‘Fundación Ramón Areces’ grant to the Centro de Biología Molecular “Severo Ochoa”
- Comisión Interministerial de Ciencia y Tecnología. Grant Number: PM98-003, SAF2001-0544
- 1997. The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype? Hum Mol Genet 6:695–707. , , , , , , , , , , , , , , , , , , .
- 1995. Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly and stability of MCAD enzyme. J Biol Chem 270:10284–10290. , , , , , , , , , , , .
- 1997. Relationship between mutation genotype and biochemical phenotype in a heterogeneous Spanish phenylketonuria population. Eur J Hum Genet 5:196–202. , , , , , , , , , , , .
- 1999. Genetic and phenotypic aspects of phenylalanine hydroxylase deficiency in Spain: molecular survey by regions. Eur J Hum Gen 7:386–392. , , , , , , , , , , , , , .
- 1991. Aberrant splicing of phenylalanine hydroxylase mRNA: the major cause for Phenylketonuria in parts of Southern Europe. Genomics 11:242–946. , , , , , .
- 1995. Molecular basis of phenylketonuria and a correlation between genotype and phenotype in a heterogeneous southeastern US population. Pediatrics 97:512–516. , , , , , , , .
- 1997. Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. Nat Struct Biol 4:995–1000. , , , , , .
- 1999. The structural basis of phenylketonuria. Mol Genet Metab 68:103–125. , .
- 2001. A structural hypothesis for BH4 responsiveness in patients with mild forms of hyperphenylalaninaemia and phenylketonuria. J Inherit Metab Dis 24:213–230. , .
- 1999. Structural Iisight into the aromatic amino acid hydroxylases and their disease-related mutant forms. Chem Rev 99:2137–2160. , .
- 1998. Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. J Biol Chem 273:16962–16967. , , , .
- 2000. Expression analysis of phenylketonuria mutations: effect on folding and stability of the phenylalanine hydroxylase protein. J Biol Chem 275:29737–29742. , , , .
- 2001a. Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine. Am J Hum Genet 68:1353–1360. , , , .
- 2001b. In Vitro Expression of 34 naturally occurring mutant variants of phenylalanine hydroxylase: correlation with metabolic phenotypes and susceptibility toward protein aggregation. Mol Genet Metab 72:132–143. , , , .
- 2001. The role of chaperone-assisted folding and quality control in inborn errors of metabolism:protein folding disorders. J Inherit Metab Dis 24:189–212. , , , , , .
- 1998. A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. Am J Hum Genet 63:71–79. , , , , , , , , , , , , , , , .
- 2000. Structural interpretation of mutations in phenylalanine hydroxylase protein aids in identifying genotype-phenotype correlations in phenyl-ketonuria. Eur J Hum Genet 8:683–696. , , .
- 1995. Comparison between medium-chain acyl-coA dehydrogenase mutant proteins overexpressed in bacterial and mammalian cells. Hum Mutat 6:226–231. , , , , , , , , .
- 1999. Structural basis of autoregulation of phenylalnine hydroxylase. Nat Struct Biol 6:442–448. , , , , , , , , .
- 1999. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. J Pediatr 135:375–378. , , , , , , , , , .
- 2001. Understanding human disease mutations through the use of interspecific genetic variation. Hum Mol Genet 10:2319–2328. , .
- 2003. PAHdb 2003: what a locus-specific knowledgebase can do. Hum Mutat 21:333–344. , , , , , , , , , , .
- 2001. Unfolding the role of chaperones and chaperonins in human disease. Trends Genet 17:528–535. , .
- 2001. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Dutch neonates. J Inherit Metab Dis 24:352–358. , , , , , , , , , , , , .
- 1997. The molecular chaperone Hsc70 assists the in vitro folding of the N-terminal nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator. J Biol Chem 272:25421–25424. , , , .
- 1999. Missense mutations in the phenylalanine hydroxylase gene (PAH) can cause accelerated proteolytic turnover of PAH enzyme: a mechanism underlying phenylketonuria. J Inherit Metab Dis 22:208–212. , , , , .
- 2000. Characterization of phenylketonuria missense substitutions, distant from the phenylalanine hydroxylase active site, illustrates a paradigm for mechanism and potential modulation of phenotype. Mol Genet Metab 69:101–110. , , , .
- 2003. How PAH gene mutations cause hyperphenylalaninemia, and why mechanism matters: insights from in vitro expression. Hum Mutat 21:357–369. .