Frequency of fragile-x in x-linked mental retardation

Fragile X syndrome [FXS] is the most common form of inherited mental retardation and accounts for about one third of all cases of X linked mental retardation [XLMR]. It is inherited as an X-linked dominant trait with a fragile site at Xq27.3 locus named fragile X mental retardation gene [FMR-1]. The FMR-1 protein is widely expressed, with the highest expression in brain, testes, ovaries, esophagus, thymus, eye and spleen. This study was conducted on twenty mentally retarded boys aged 8.5 +/- 3.84 years, attending the genetic clinics at Menoufiya University hospitals. They represented 11 families. All patients were subjected to detailed history, family pedigree, anthropometric measurements, thorough clinical examination with clinical scoring for the 13 items fragile X checklist, IQ assessment, routine investigations and cytogenetic studies which included conventional karyotyping using G banding and cytogenetic analysis for fragile X detection. Positive consanguineous marriage was found in 15% of our studied cases. Nine families out of total eleven families had positive family history most of them were second degree relative males through maternal cousins. Craniofacial abnormalities included high arched palate in 65% of patients, large ears in 55%, prominent forehead in 45% and elongated face and abnormal teeth in 30% for each. Speech problems were present in 75% and hyperactivity in 55% of patients. Sixty five percent had mild mental retardation [IQ= 50-70%].By applying the clinical scoring fragile X checklist, it was found that 3 patients [15%] had score more or equal to 19 and 3 [15%] had score from 16 to less than 19, while 14 [70%] had score less than 16. As regards cytogenetic studies, 80% of our patients had normal karyotyping [46 XY] while four cases [20%] had positive fragile site on X-chromosome of whom two cases from the same family had 46, Y, Frg [X] [q27.3], while the other two cases, also from a single family, had inversion of Y chromosome beside positive fragile X chromosome site 46, Fra[X] [q27.3], inv [Y]. So, in a child with isolated mental retardation or autism of unknown etiology with considerable fragile X dysmorphic features or established family history of fragile X syndrome, chromosomal study that identifies the fragile site at Xq27.3 in addition to other cytogenetic abnormalities could be useful or early diagnosis and intervention by a special services team

study of DNA damage and antioxidant defense in the peripheral leucocytes of diabetic mothers and their newborn infants

Oxidative stress plays a key direct and indirect role in the pathogenesis of several diabetes and pregnancy related complications in both diabetic mothers and their infants. Forty women and their newborn infants divided into two groups were studied. Group I included 20 diabetic women and their newborn infants. Group II consisted of 20 clinically healthy women and their twenty newborns as controls. All involved mothers and newborns were subjected to detailed history, thorough clinical examination, routine laboratory investigations, imaging studies, and specific laboratory investigations including assessment of glycosylated hemoglobin [HbA1C] for diabetic mothers, and erythrocyte antioxidant enzymes [superoxide dismutase, catalase and glutathione peroxidase] and DNA fragmentation assay for mothers and neonates of both groups. It was found that 25% of the diabetic women had diabetic complications. About 1/3 of the newborn infants of diabetic mothers were large for gestational age, 10% of them had major congenital anomalies [cyanotic heart disease and meningomyelocele] and 15% of them died. Levels of erythrocytes glutathione peroxidase and catalase were significantly lower in diabetic mothers and their infants than those in nondiabetic mothers and their infants. DNA damage, mainly in the form of apoptosis was present in diabetic mothers and their infants [60% and 50% respectively]. There was a significant difference between the values of maximal optical density at 200bp and 600bp between both groups. Comparison between diabetic mothers with and without diabetic complications as regards HbA1C, antioxidants and DNA damage showed that erythrocytes catalase was significantly lower in those with complications [means 366 +/- 54 units/g Hb, 426.3 +/- 45.7 units/g Hb respectively] as a possible explanation for complications in this group. There was a significant negative correlation between HbA1C of diabetic mothers [i.e. diabetic control] and glutathione peroxidase level [i.e. antioxidant defense] in their infants. A significant negative correlation was found between DNA damage and erythrocytes antioxidant [Superoxide dismutase in diabetic mothers, and glutathione peroxidase in their infants]. It can be concluded that hyperglycemia causes a significant reduction of antioxidant capacity [reduced catalase and glutathione peroxidase] in the diabetic mothers and their infants compared with controls and this may be the cause of increased DNA damage observed in these individuals which may lead to the development of diabetic complications in the pregnant mothers and congenital anomalies in their infants. It is recommended to maintain a good control of diabetes and combat oxidative stress to lessen diabetic complications in pregnancy and to avoid congenital anomalies