Connecting mutant phenylalanine hydroxylase with phenylketonuria.
OBJECTIVE
The building of a quantitative relationship between genotype and phenotype would be great helpful for better clinical monitoring, diagnosis, prognosis and treatment. As the phenylketonuria is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase, in this study we build a descriptively quantitative relationship between mutant phenylalanine hydroxylase and classifications of phenylketonuria.


METHODS
The amino-acid distribution probability is used to quantify the phenylalanine hydroxylase and its mutants, the cross-impact analysis is used to couple mutant phenylalanine hydroxylase and classifications of phenylketonuria, and the Bayesian equation is used to compute the probability that the phenylketonuria can be classified under mutations.


RESULTS
The results show that the patient has more than 0.9 chance of being phenylketonuria when a new mutation occurs in phenylalanine hydroxylase.


CONCLUSIONS
The built relationship paves the way for modeling of this type relationship for better clinical monitoring, diagnosis, prognosis and treatment.
Yan
Shaomin
S
Guangxi Academy of Sciences, Nanning, China.
Wu
Guang
G
D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000737:chemistry* / Q000235:genetics*; D010661:Phenylketonurias / Q000201:enzymology* / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*
D010651:Phenylalanine Hydroxylase
Protein Pept Lett. 2008;15(4):341-5
18473944
J Hist Neurosci. 2003 Mar;12(1):44-54
12785112
Hum Mutat. 2001 Jun;17(6):523
11385716
Lancet. 1974 Sep 7;2(7880):540-4
4140266
Hum Mutat. 2000;15(3):254-60
10679941
Biochem Biophys Res Commun. 2004 Aug 20;321(2):313-9
15358177
Protein Pept Lett. 2007;14(5):465-70
17584172
Eur J Pediatr. 1988 May;147(4):361-7
3396592
Hum Mutat. 1994;4(3):229-31
7833954
Protein Pept Lett. 2006;13(1):101-7
16454678
Mol Genet Metab. 2001 Jul;73(3):280-4
11461196
Am J Hum Genet. 1998 Jul;63(1):71-9
9634518
Mol Genet Metab. 2000 Mar;69(3):195-203
10767174
Am J Hum Genet. 2001 Jun;68(6):1353-60
11326337
Genet Mol Res. 2006 Mar 31;5(1):33-44
16755495
Am J Hum Genet. 2000 Jun;66(6):1729-35
10793008
J Nutr. 2004 Jun;134(6 Suppl):1600S-1604S; discussion 1630S-1632S, 1667S-1672S
15173437
J Pediatr. 2002 May;140(5):502-6
12032513
Curr Med Chem. 2004 Aug;11(16):2105-34
15279552
Genetica. 1998;102-103(1-6):41-7
9720270
Hum Mutat. 2001 Feb;17(2):122-30
11180595
J Pediatr. 1999 Sep;135(3):375-8
10484807
Dev Med Child Neurol. 1979 Jun;21(3):311-20
467815
Med Sci Monit. 2003 Mar;9(3):CR142-6
12640344
Hum Mutat. 2003 Apr;21(4):370-8
12655546
Pediatrics. 2000 Jan;105(1 Pt 1):89-103
10617710
Hum Mutat. 1998;12(5):344-54
9792411
Protein Pept Lett. 2007;14(2):191-6
17305607
Hum Mutat. 1998;11(1):4-17
9450897
J Mol Model. 2002 May;8(5):191-8
12111387
J Biochem Mol Biol Biophys. 2002 Dec;6(6):407-14
14972796
Amino Acids. 2008 Jan;34(1):81-90
17721674
Hum Mutat. 1996;8(3):276-9
8889590
Neuropsychol Rev. 2007 Jun;17(2):91-101
17410469
Biochem Biophys Res Commun. 2005 Jan 14;326(2):475-82
15582602
Acta Pharmacol Sin. 2006 May;27(5):513-26
16626505
Hum Mutat. 2003 Apr;21(4):333-44
12655543
Hum Mutat. 1998;Suppl 1:S123-4
9452062
Mol Divers. 2007 Aug-Nov;11(3-4):131-40
18283552
Alcohol Alcohol. 2000 Jan;35(1):55-9
10684778
Protein Pept Lett. 2006;13(2):143-8
16472076
Protein Pept Lett. 2006;13(10):971-6
17168817
Clin Biochem. 2004 Dec;37(12):1083-90
15589814
Med J Aust. 1971 Feb 13;1(7):378-83
5553139
Protein Pept Lett. 2008;15(2):144-52
18289106
Arch Pediatr Adolesc Med. 2006 Mar;160(3):302-9
16520451