Genotype-phenotype correlations analysis of mutations in the phenylalanine hydroxylase (PAH) gene.
The aims of our research were to define the genotype-phenotype correlations of mutations in the phenylalanine hydroxylase (PAH) gene that cause phenylketonuria (PKU) among the Israeli population. The mutation spectrum of the PAH gene in PKU patients in Israel is described, along with a discussion on genotype-phenotype correlations. By using polymerase chain reaction/denaturing high-performance liquid chromatography (PCR/dHPLC) and DNA sequencing, we screened all exons of the PAH gene in 180 unrelated patients with four different PKU phenotypes [classic PKU, moderate PKU, mild PKU, and mild hyperphenylalaninemia (MHP)]. In 63.2% of patient genotypes, the metabolic phenotype could be predicted, though evidence is also found for both phenotypic inconsistencies among subjects with more than one type of mutation in the PAH gene. Data analysis revealed that about 25% of patients could participate in the future in (6R)-L: -erythro-5, 6, 7, 8-tetrahydrobiopterin (BH4) treatment trials according to their mutation genotypes. This study enables us to construct a national database in Israel that will serve as a valuable tool for genetic counseling and a prognostic evaluation of future cases of PKU.
Bercovich
Dani
D
MIGAL, Galilee Technology Center, Human Molecular Genetics and Pharmacogenetics Laboratory, Kiryat Shmona, Israel. danib@migal.org.il.|Tel-Hai Academic College, Upper Galilee, Israel. danib@migal.org.il.
Elimelech
Arava
A
MIGAL, Galilee Technology Center, Human Molecular Genetics and Pharmacogenetics Laboratory, Kiryat Shmona, Israel.
Zlotogora
Joel
J
Department of Genetic Community, Public Health Services, Health Ministry and Hebrew University, Jerusalem, Israel.
Korem
Sigal
S
MIGAL, Galilee Technology Center, Human Molecular Genetics and Pharmacogenetics Laboratory, Kiryat Shmona, Israel.|Tel-Hai Academic College, Upper Galilee, Israel.
Yardeni
Tal
T
MIGAL, Galilee Technology Center, Human Molecular Genetics and Pharmacogenetics Laboratory, Kiryat Shmona, Israel.
Gal
Nurit
N
Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
Goldstein
Nurit
N
Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
Vilensky
Bela
B
Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
Segev
Roni
R
Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
Avraham
Smadar
S
Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
Loewenthal
Ron
R
Tissue Typing Unit and Safra Children Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Schwartz
Gerard
G
Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
Anikster
Yair
Y
Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D010649:Phenylalanine / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000235:genetics* / Q000502:physiology; D010661:Phenylketonurias / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase