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.
Clin Biochem. 2010 Jan;43(1-2):76-81. doi: 10.1016/j.clinbiochem.2009.09.018. Epub 2009 Sep 26.
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.
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.
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.
The results provide important information on the distribution of PKU mutations in this Mediterranean area gaining insight into the genetic epidemiology of the disease.
不同国家对苯丙酮尿症（PKU，MIM#261600）分子基础的了解，为在每个群体中开展特定和合理的突变检测策略以及实施适当的饮食和辅助因子治疗提供了相关信息。摩洛哥人群中尚无相关数据。
本研究通过变性梯度凝胶电泳（DGGE）进行突变扫描的遗传分析，并对来自摩洛哥的 20 个不同 PKU 家系进行直接测序。我们还研究了在西班牙新生儿筛查计划中发现的 7 名居住在西班牙的摩洛哥 PKU 患者。
第一组样本的突变谱包括 8 种不同的变化，其中一种 p.K85X 是新发现的。最常见的突变是 62.5%的突变染色体中发现的框移突变 p.G352fsdelG。其他变化（p.R176X、IVS10nt-11 g>a、p.W120X、p.A165T、p.R243X 和 p.R243Q）分别在 2 或 3 个突变等位基因中发现。所有检测到的突变均根据患者的经典表型为严重突变。在居住在西班牙的 7 名患者中，我们检测到 4 种严重突变（p.G352fs、p.R176X、Y198fs 和 Exon3del），以及在 3 名轻度高苯丙氨酸血症（MHP）患者中发现的 p.A403V、p.S196T、p.D145V 和 p.R408Q 等较轻微的变化，以及在一名轻度 PKU 患者中发现的新型 p.L258P。
这些结果为了解该地中海地区 PKU 突变的分布情况提供了重要信息，深入了解了该疾病的遗传流行病学。
