Gene mutations in Wilson disease in Egyptian children: report on two novel mutations

Wilson disease [WD] is an autosomal recessive disorder, caused by defects in copper-transporting P-type adenosine triphosphatase [ATPase] encoded by the ATP7B gene, resulting in the deposition of copper in the liver and brain with significant disability or death if left untreated. An available regimen of treatment gives hope to those predisposed to the disease if diagnosed early. The objective of this study was to determine the frequency of the most common European mutation [p.H1069Q] in Egyptian children with WD, in addition to screening for previously reported mutations in the Egyptian patients in our selected group. Direct DNA sequencing was applied to exons [13, 14, 18, and 19] of the ATP7B gene for 19 patients previously diagnosed with WD. Then DNA sequencing and pedigree analysis were performed in the families of the patients showing variations in their results for the purpose of family screening and carrier detection. Six out of 19 patients were studied with their families [three families]. We identified five variants of which two were novel among the studied patients. One of the novel variants was synonymous substitution [p.A1074A] in 16% of patients and the other was predicted to be missense disease-causing mutations [p.T1076I] in 16% of patients, and three previously published mutations p.H1069Q were detected in 5% of patients, p.P1273Q in 10% of patients, and a silent variant p.A1003A in 26% of patients. Screening for the two exons 14 and 18 of the ATP7B gene is important in Egyptian patients especially in suspected patients without hepatic manifestations

Vitamin D receptor [VDR] gene polymorphism and risk of osteoporosis in Egyptian post menopausal women

Identifying people at risk of osteoporosis is very important, as prevention is possible. Because genetic factors were shown to have a great influence on osteoporosis susceptibility, their study may be of great help in targeting high-risk individuals. In this work, we studied the association between VDR gene polymorphism and bone mineral density in postmenopausal Egyptian females. 45 Egyptian postmenopausal women [57 +/- 4.6 years] were studied. Bone mineral density was measured at the lumbar spines, the hip, and the lower radius using dual energy X-ray absorptiometry. Ten of the studied patients [22%] had osteoporosis [T or z scores < -2.5]; 21 [47%] had osteopenia [T or z scores -1 to -2.5]; and 14[31%] were normal [T or z scores > -1]. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in these four VDR gene loci. The BsmI Bb genotype distribution was significantly higher in the normal postmenopausal women [42.9%] than osteopenic women [4.8%] [p value < 0.002]. The TaqI [T] allele was significantly higher in the normal group [68.0%] than the osteopenic group [45.0%] and TaqI [t] which was significantly higher in the osteopenic group [55.0%] than the normal group [32.0%] [p=0.031 for both], otherwise, there was no significant difference in the distribution of other VDR genotypes in relation to bone density measurement. The higher distribution of the VDR BsmI Bb and TaqI T genotype in the normal postmenopausal than osteopenic women may reflect a protective role, on the other hand, TaqI t allele may be associated with lower bone mineral density in postmenopausal Egyptian females

Serum levels of matrix metalloproteinases in type II diabetes mellitus

Hyperglycemia is associated with excessive non-enzymatic glycosylation of the glomerular matrix thus contributing to the pathogenesis of diabetic nephropathy. Matrix metallopoteinases [mmp[s]] are responsible for matrix degradation. This study was conducted to unvestigate the potential diagnostic value of serum levels of two of the known mmp[s]], namely mmp-1 and mmp-2 in type ii diabetes and their relationship to vascular complications. This study was concluted on 30 female type ii niddm diabetes mellitus [dm] patients recruited from the diabetic clinic, kasr al aini hospital, cairo university. A control group including 10 apparently healthy age matched females with no family history of diabetes was also studied. All patients were subjected to full history taking and full clinical examination. Laboratory investigations included fasting blood sugar, liver function tests, kidney functions, lipid profiles, glycosylated hemoglobin, according to which, patients were divided into 2 groups, fairly and poorly controlled and microalbuminuria, according to which, patents were divided into with and without diabetic nephropathy. Mmp-1 and mmp-2 were measured using an elisa technique. The ages of the patients under study ranged from 40-55, with a mean of 48.83 +/- 4.36. The duration of diabetes ranged between 1-20 years with a mean of 110-170 with a mean of 129.33 +/- 18.56 and their diastolic blood pressure ranged from 60-110 with a mean of 79.33 +/- 8.68. The mean serum mmp-1 level was significantly higher 16.63 +/- 9.13 and 5.48 +/- 2.37 respectively [p= < 0.01]. Mmp-1 was significantly higher in patients with nephropathy compared to controls, however it was significantly decreased than its mean value in patients without nephropathy 14.3 +/- 8.55 and 21.3 +/- 8.83 respectively [p= < 0.05]. The mean serum mmp-1 level was significantly higher in the poorly controlled and fairly controlled diabetics [16.71 ng/ml +/- 9.23 and 16.52 ng/ml +/- 9.37] as compared to the control group [5.48 ng/l +/- 2.37] [p= < 0.01]. The mean serum mmp-1 was significantly higher in the hypertensive group compared with control group 13.49 +/- 8.52 and 5.48 +/- 2.37 respectively [p= < 0.01]. On the other mean serum mmp-2 level was significantly reduced in hypertensive cases compared to the non-hypertensive ones 197.4 +/- 56.76 and 24.741 +/- 57.53 respectively [p= < 0.05]. The mean mmp-2 levels also showed a positive correlation with the diastolic blood pressure [r=0.756, p< 0.01]. Mmp-1 serum levels may be implicated in the complications of DM

Correlation study between cord blood trace elements and anthropometric measures of the newborn

This work was designed to assess the serum zinc and copper levels in pregnant Egyptian ladies at delivery and in their corresponding offspring as well as to study the effects of these elements on intrauterine fetal growth. Thirty full term small for gestational age neonates [SGA] were studied together with their mothers at delivery. They were compared to thirty eight full term appropriate for gestational age [AGA] neonates as well as their mothers. Mothers of both groups of studied neonates were compared to 20 non pregnant ladies as regards serum zinc and copper level. All cases and controls were subjected to detailed history taking from mothers and all deliveries were attended. All babies were examined to exclude acute and chronic complications. Anthropometric measurements were taken at birth. Laboratory investigations including assessment of serum zinc and copper levels by atomic absorption spectrophotometry were performed. The results proved that serum zinc levels were significantly lower in the group of SGA babies as well as their mothers than the group of AGA babies and their corresponding mothers. Similarly, both groups of delivered mothers had significantly lower zinc level than non pregnant ladies. Study of the copper levels in mothers and their neonates showed a tendency to increased levels beyond the normal upper limit in the group of both mothers of SGA and AGA babies with no such increase in their neonates. Our study confirmed that zinc status of mothers during pregnancy strongly affects the intrauterine growth of fetuses. This effect was mainly on weight, resulting in retardation of their growth in cases of mothers who suffered form hypozincemia. The end result was delivery of small for gestational age babies