Mutation analysis of phenylketonuria patients from Morocco: High prevalence of mutation G352fsdelG and detection of a novel mutation p.K85X |
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| Authors: | Saloua Dahri Lourdes R Desviat Belén Pérez Fátima Leal Magdalena Ugarte Layachi Chabraoui |
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| Institution: | 1. 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;2. Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) Madrid, Spain;1. Ophthalmology A Department, hôpital des spécialités de Rabat, Morocco;2. Faculty of Medicine and Pharmacy, BP 6203, Morocco;3. Mohammed V – Souissi University, BP 8007, Morocco;1. RTI International, Research Triangle Park, NC;2. University of North Carolina at Chapel Hill, Chapel Hill,NC;3. Duke University School of Medicine, Durham, NC;4. North Carolina State Laboratory of Public Health, Raleigh, NC;5. Nationwide Children''s Hospital, Division of Ambulatory Pediatrics, Columbus, OH;1. National Institute of Hygiene, Ministry of Health, Rabat, Morocco;2. Epidemiological and Diseases Control Department, Ministry of Health, Rabat, Morocco;3. Viral Gastroenteritis Division, Centers for Diseases Control and Prevention, Atlanta, GA, United States;4. World Health Organization, Regional Office for the Eastern Mediterranean, Cairo, Egypt;5. Nutrition Unit, Pediatric Unit III, Children Hospital, Rabat, Morocco;6. Faculty of sciences Agdal, Mohamed V University, Rabat, Morocco |
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| Abstract: | 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.Design and 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.Conclusion:The results provide important information on the distribution of PKU mutations in this Mediterranean area gaining insight into the genetic epidemiology of the disease. |
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