Prenatal diagnosis of classical phenylketonuria in fifteen egyptian families

Phenylketonuria [PKU] is one of the most common inborn errors of metabolism; if not diagnosed early and treated by special diet intervention mental retardation is the outcome. Seeking prenatal diagnosis, counseling and diet management is curial for families with PKU. This study reports prenatal diagnosis in 15 Egyptian families with classical PKU. Two different techniques were performed based on the molecular data available from probands. Targeted screening of mutations using RFLP analysis identified three mutations, IVS10-11G/A, R261Q and R252W mutations in five fetuses. Direct sequencing revealed R261X mutation one fetus and Y198_E205>cfs mutation in one allele in another fetus. Indirect linkage analysis by VNTR and STR markers identified 4 affected, two carrier and two normal fetuses. In conclusion, prenatal diagnosis of PKU is an effective tool for prevention of mental retardation and provision of enough time for proper planning and effective management. The molecular tools pursued were efficient and reliable in all families providing them the opportunity of choosing different management strategies

Phenylalanine hydroxylase VNTR polymorphism patterns among Egyptian normal and phenylketonuric subjects

Analysis of the polymorphic variable number of tandem repeats [VNTR] is a powerful tool for detection of DNA variation among normal individuals within a population, as well as testing linkage to disease-underlying mutations in various ethnic groups. Phenylketonuria [PKU] is caused by mutations in the phenylalanine hydroxylase [PAH] gene, which has a VNTR region at the 3 end. In this work, we report on the PAH VNTR polymorphism patterns among a sample of the Egyptian population and a large number of PKU cases. The study included 77 normal subjects and 87 phenylketonuric probands. Genomic DNA was extracted from leukocytes using the salting out technique. DNA amplification using specific primers and the polymerase chain reaction was used to detect the various VNTR patterns. The VNTR heterozygosity index was 56% and 21% in the normal and PKU groups, respectively. The VNTR homozygosity index was comparably high in patients with IVS10-11 G>A and R261Q mutations, [i.e. > 80%]. An unusually high prevalence of the 8-RU and 10-RU alleles among non-IVS1011 G>A/non-R261Q PKU cases was noted. The VNTR patterns in both normal and PKU-affected Egyptians were highly heterogeneous. Moreover, both IVS10-11 G>A and R261Q showed previously unreported VNTR patterns. In conclusion, the study of PAH VNTR allele patterns among normal and PKU-affected Egyptian subjects has confirmed the high heterogeneity of the normal Egyptian population as well as the PKU patients

Common FGFR3 gene mutation is detected in Egyptian patients with achondroplasia phenotype

In this study, the identification of a recurrent missense mutation [G 1138 A] in the transmembrane domain of the fibroblast growth factor receptor-3 [FGFR3] protein with glycine substituted with arginine at a residue 380 [G380R] was reported. It was shown that the mutant genotype was segregated in eight sporadic cases [out of eleven] of achondroplasia patients. The identified common mutation was in the heterozygous state in all instances, the homozygous form of the mutation was not observed. The G380R was not identified in the three cases in whom the clinical and radiological features of achondroplasia were shown, indicating the possibility of the presence of another, less frequent, FGFR3 gene mutation that might account for the ACH- phenotype and need a further delineation. In this analysis, the presence of the G380R mutation in a variety of Egyptian ACH patients was confirmed, who had not been previously reported on