Molecular characterization of X chromosome fragility in idiopathic mental retardation

Background: Fragile X syndrome [FXS] is the most common form of inherited mental retardation. Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients is relatively high. Cytogenetic diagnosis of FXS is unreliable since it is ineffective for the diagnosis of premutated males or females. Proper molecular diagnosis is a pre-requisite for providing proper counseling advice

Subjects and methods: Sixty-four males with idiopathic mental retardation, ranging in age from 4.2 to 19 years [10.92+/- 4.00] were clinically pre-selected, based on scoring protocol comprising eight features of the syndrome, before molecular testing. A rapid polymerase chain reactionbased screening was applied for detection of expanded FMR1 alleles. Samples that did not yield the normal band lengths were subjected to a second PCR screen. The secondary screen utilizes a chimeric primer demonstrating the presence or absence of an expanded allele

Results: Amplification of FMRI gene by PCR of tested patients revealed that 8 cases [12.5%] have full mutation and 6 cases [9.4%] have premutation. A wide range of Fra X-scoring ranging from 1 to 7 features was detected in examined cases. Significant clinical features included large prominent ears, hyperextensibility of joints and macroorchidism in post pubertal males

Conclusions: A simplified checklist of fragile X should be used for patients with idiopathic MR and those patients above score 3 should be tested for FXS. The diagnostic assay may be used as a screening method for fragile X syndrome being rapid and cost effective compared to other techniques. In addition, screening of all relatives of proven patients should be performed to detect clinically unidentified cases for provision of proper counseling and optimal management of detected cases

Genotyping of mannose-binding lectin [MBL2] codon 54 and promoter alleles in Egyptian infants with acute respiratory tract infections

MBL2 gene polymorphisms affect serum concentration of mannose-binding lectin and are associated with infectious conditions. Acute respiratory tract infections are among the most prevalent infections in childhood with the highest incidence among children younger than 2 years. This study aimed at correlation between the occurrence of acute respiratory tract infections and the prevalence of MBL2 gene codon [54] and promoter variants among the Egyptian infants in the study. This case-control study included 25 neonates [0.21 +/- 0.19 months], 25 infants [9.65 +/- 8.5 months] with acute respiratory tract infection and normal control group. CBC, CRP and chest X-ray were done. DNA was extracted from peripheral blood. Genotypes of MBL gene codon 54-exon 1[G54D] were identified by PCR-RFLP analysis. MBL2 promoter genotyping was performed by allele-specific polymorphisms at -550 [H/L] and - 221[X/Y]. Incidence of LX promoter haplotype among the patients was [58%] [p < 0.05]. Homo-zygosity for codon [54] allele A [high expression activity] among patients was [72%] [p > 0.05]. Heterozygote codon 54 A/B genotype appeared more in patients [18%] [p < 0.05]. Mutant genotype [too low expression activity] was more in patients but the difference was insignificant. Collectively the mutant allele [glycine to aspartic acid, allele B] appeared in 28% of patients compared to 20% in control [p > 0.05]. YA/XA heterozygote promoter genotype was more prevalent among patients group [44%] [p < 0.05]. Low-expression promoters [XA/B] and [B/B] appeared more in the patients [20%] compared to [12%] among control group [p > 0.05]. Among ICU neonates, LX promoter was the most prevalent among all grades of respiratory distress [39.13%] followed by LY allele [34.78%]. In the infants group, LY allele was [52.1%] with equal distribution of LY and HY [23.91% each]. Although there is a significantly increased incidence of LX promoter coding for low serum MBL concentrations among the ARTI patients; the YA/XA heterozygote promoter genotype was more prevalent over the homozygote mutant genotype. Also, the heterozygote codon 54 A/B genotype was more prevalent in the group of patients compared to the control. This may be an example of heterosis [heterozygote advantage] which may support the concept of balanced polymorphism