Mutation analysis of phenylketonuria patients from Morocco: high prevalence of mutation G352fsdelG and detection of a novel mutation p.K85X.
OBJECTIVE
The knowledge of the molecular basis of the Phenylketonuria (PKU, MIM# 261600) in different countries provides relevant information for undertaking specific and rational mutation detection strategies in each population and for the implementation of adequate dietary and cofactor treatment. There are no data available in Moroccan population.


METHODS
In this work we describe the genetic analysis by mutation scanning using denaturing gradient gel electrophoresis (DGGE) and subsequent direct sequencing of 20 different PKU families from Morocco. We have also included the study of 7 Moroccan PKU patients living in Spain detected by the Spanish newborn screening program.


RESULTS
The mutational spectrum in the first sample included eight different changes, one of them, p.K85X, was novel. The most common mutation was the frame shift change p.G352fsdelG identified in 62.5% of the mutant chromosomes studied. Other changes (p.R176X, IVS10nt-11 g>a, p.W120X, p.A165T, p.R243X and p.R243Q) were identified, respectively, in 2 or 3 mutant alleles. All detected mutations were severe according to the classical phenotype of the patients. In the 7 patients living in Spain we have detected 4 severe mutations (p.G352fs, p.R176X, Y198fs and Exon3del) and also milder changes such as p.A403V, p.S196T, p.D145V and p.R408Q detected in 3 mild hyperphenylalaninemia (MHP) patients and a novel p.L258P found in a mild PKU patient.


CONCLUSIONS
The results provide important information on the distribution of PKU mutations in this Mediterranean area gaining insight into the genetic epidemiology of the disease.
Service de Biochimie, Centre d'Etudes des Maladies Héréditaires du Métabolisme, Hôpital d'Enfants de Rabat et Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Moroccco.
Saloua
S
Dahri
Lourdes R
LR
Desviat
Belén
B
Pérez
Fátima
F
Leal
Magdalena
M
Ugarte
Layachi
L
Chabraoui
D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009018:Morocco / Q000453:epidemiology; D009154:Mutation; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D013030:Spain
D010651:Phenylalanine Hydroxylase