Autosomal dominant genetic disorders among patients attending the genetic clinic of medical research institute

A total number of 1600 patients referred to the Genetic Clinic, Medical Research Institute, Alexandria University, were assessed to determine the frequency of autosomal dominant disorders. It was found that 5.25% [84 patients] had autosomal dominant disorders. Bone dysphasia/short stature were the most common disorders 47.60% [40/84], where half of them were achondroplasia cases. Osteogenesis imperfect a type I was detected in 10 cases. Dysmorphic autosomal dominant syndromes were observed in 35.70% [30/4]. Syndromes with craniosynostosis were more frequent [26/84]. Encountered in this study also, 9 cases [10.70%] with Hamartoses [6 cases had Neurofibromatosis type I and II and 3 with Tuberous Sclerosis]. Skin disorders were reported in 6.0% cases [5/84]. Positive family history were observed among cases with Achondroplasia, Apert, Crouzon, Albright hereditary osteodystrophy, Neurofibromatosis type II and Waardenburg syndrome. The remainder was sporadic due to fresh mutations especially in cases with older paternal age mainly in achondroplasia, Aped and Crouzon syndromes. The chronic nature of genetic disorders requires life long medical attention, expensive supportive and symptomatic therapy, and specialized care

LMNA gene polymorphism [1908/CT] and indices of obesity in a sample of Egyptian females

Nuclear Lamins A and C are encoded by LMNA gene and present in terminally differentiated cells. The LMNA gene polymorphism [1908C/T] has been reported to be associated with adipose tissue metabolism and obesity indices in some populations, suggesting that this polymorphism may increase the risk of obesity. This study was conducted to estimate the C and T allele frequencies of LMNA gene polymorphism [1908], and to investigate the association of T-allele with obesity in a sample of Egyptian obese females. One hundred and forty Iwo obese females [BMI>30Kg/m[3]] and 100 age matched non obese females [BMI

Ghrelin arg Arg5 1Gln polymorphism in Egyptian patients with type II diabetes mellitus

Ghrelin is a peptide hormone known to play a role in glucose homeostasis; therefore functional variants of the human ghrelin gene could contribute to the genetic susceptibility to diabetes or may modulate some aspects of the glucose intolerance phenotype. The study aimed at investigating the differences in the frequencies of Arg51Gln polymorphisms among Egyptian patients with type II diabetes and healthy control subjects and at verifying whether this polymorphism could influence the diabetes phenotype. One-hundred-four Egyptian type II diabetic patients attending the Medical Research Institute were enrolled into the study. Clinical data concerning medical and family history were collected by a clinical interview. Another group of 100 non-diabetic apparently healthy subjects were included to compare the Arg51Gln genotypes frequencies. The ghrelin Arg51Gln polymorphism was studied by PCR restriction fragment length polymorphism method in the diabetic and control subjects. The metabolic profile of the diabetic patients was also analyzed. A chi[2] test was adopted to compare the ghrelin Arg51Gln genotype and allele frequencies among the two groups. Moreover, in order to test whether the differences in phenotypic variables between the patient groups were influenced by ghrelin genotype, ANOVA test was performed. The frequency of the 51 gln heterozygotes and homozygotes were significantly higher in the patients group than in the control sample [chi[2] =8.962, P= 0.0113]. Also, the 51 Gln allele frequency was higher in the patients than in the control group [q=0.27 and q=0.14, respectively]; a difference that was found statistically significant [chi[2] =5.185, P = 0.022]. The fasting blood sugar and triglycerides levels were higher in patients carrying the ghrelin 51 Gln allele than in those with the wild allele [statistically significant, P=0.014 and p=0.004, respectively]. No statistically significant difference was observed between the total cholesterol, HDL and LDL cholesterol concentrations among these two groups. There is a significant positive association between ghrelin 51 Gln polymorphism and type II diabetes in the Egyptian population. Further studies are warranted to elucidate the role of ghrelin in the development of this disease

association of angiotensinogen converting enzyme [ACE] insertion/ deletion polymorphism with preeclamptic women in Alexandria - Egypt

Plasma and tissue ACE [angiotensin converting enzyme] activities are under genetic control. Increased ACE activity due to the deletion polymorphism of the ACE gene is associated with diseases that exhibit endothelial disturbance. Studies in various ethnic group have shown contradictory evidence on the association of ACE insertion/deletion [I/D] polymorphism with preeclampsia [PE]. In this study, we studied the potential association of I/D polymorphism of the ACE gene with PE. One hundred and seventeen preeclamptic women and 102 age-matched normotensive pregnant women were recruited from El Shatby Maternity Hospital Alexandria University. We performed genotyping for all the studied cases taking into account some wellknown contributing factors in PE such as maternal age, primiparity, gestational age and proteinuria. All these variables were significantly associated with PE.There was a shift in the genotype frequency distribution among preeclamptic women. The highest being for the II genotype, where the distribution of the II, ID and DD ACE genotypes was 51.3%, 26.5% and 22.2% in PE and 4.85%, 15.13% and 80.22% in normotensive subjects. The estimated frequencies of the insertion allele were 68.9% and 12.7% in PE and healthy controls respectively, while the frequencies of the deletion allele were 31.3% and 87.3% in PE and controls respectively. The present study showed that the ACE II genotype may have a predisposing effects on preeclampsia especially in younger women and/or in women with earlier gestational age .The ACE DD genotype didn't show any association with preeclampsia. The genetic susceptibility in preeclampsia needs more studies about the role of other candidate genes in addition to the ACE gene

Angiotensinogen gene [M235T] variant and pre-eclampsia in Egyptian pregnant women

Association between the angiotensinogen gene [M235T] and pre-eclampsia has been confirmed in recent studies. Pre-eclampsia is a complication of pregnancy characterized by increased vascular resistance, higher blood pressure, proteinuria and oedema that appear in the second and third trimester of pregnancy. This study aimed at investigating the relationship between M235T gene polymorphism and pregnant women with different forms of pre-eclampsia. One hundred and fifteen pre-eclamptic women and 100 normal control group were recruited and evaluated for the frequency of M235T mutation using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]. A positive association was found between maternal age over 35 years [OR = 6.67; CI: 2.09-23.59], previous family history of hypertension [OR = 3.01; CI: 1.18-7.66], previous pre-eclampsia [OR = 7.44; CI: 2.47-22.42], history of reproductive losses [OR = 53.98; CI: 3.23-90.88], fetal anomalies [OR = 8.4; CI: 1.06-180.33], and pre-eclampsia. The frequency of heterozygous carriers of M235T mutation in pre-eclampsia [19.1%] was higher than that in control [14%] but the difference was statistically non-significant. Also, the frequency of M235T mutation was higher in mild pre-eclampsia women [63.6%] compared to women with severe pre-eclampsia [36.4%], however this was statistically non-significant. This study revealed that the frequency of M235T mutation was higher within women with mild pre-eclampsia

X-linked disorders among patients with suspected genetic disorders attending the genetic clinic in Alexandria

A total of 1825 patients referred to the Genetics Clinic, Medical Research Institute, Alexandria University were assessed to determine the frequency of X-linked disorders. It was found that 3.0% [55/1825 cases; 52 males and 3 females] had X-linked disorders; 31.0% [17/55] had fragile X-syndrome 21.8% [12/55] had androgen insensitivity syndrome, 14.5% [8/55] had muscular dystrophy, 14.5% [8/55] had biochemical disorders and 18.2% [10/55] had X-linked syndromes. The frequency of consanguinity among parents of cases with X-linked disorders was 29.1%. Positive family history was detected in 29.1% of cases. These findings are crucial for geneticists and genetic counsellers in their evaluation, diagnosis, counseling and management of patients

molecular study of methylenetetrahyrofolate reductase gene in mothers of standard down syndrome patients

The observation that a lot of children with Down syndrome are born to mothers with young age made it important to identify the mechanisms involved in this young age group. It was found that DNA hypomethylation is associated with chromosomal instability and abnormal chromosome segregation. This knowledge led to the clarification of the role of enzymes involving in the methylation reaction like Methylene Tetrahydrofolate Reductase enzyme [MTHFR]. The C-T common polymorphism at nucleotide 677 [C677T], which results into an alanine to valine substitution in the MTHFR protein, caused higher thermolability and reduced enzyme activity in lymphocyte extracts. In order to verify this association, we studied the presence of the C677T polymorphism of the MTHFR gene in 50 mothers of Down syndrome children and 50 control mothers. A non-significant higher incidence of the mutant T allele in Down syndrome children mothers [6%] than in control [2%] was detected. These results do not support the presence of an increased risk of Down syndrome mothers carriers of the T allele in Egyptian population

Micronucleus assay in patients with lung cancer, chronic obstructive pulmonary disease and non-smoker control

This study included 96 male subjects; 40 patients with lung cancer, 36 patients with chronic obstructive pulmonary disease [COPD] and 20 control subjects. 25% of cases with lung cancer and 86.1% of cases with COPD had micronucleus [MN] frequency ranging <5-<15 MN/500 cytokinesis blocked [CB] binucleated cells compared with 100% in the control group. 40% of cases with lung cancer and 13.9% of cases with COPD had 15-20 MN/500 CB binucleated cells. 35% of cases with lung cancer had 20-25 MN/500 CB binucleated cells. These differences were statistically significant. In the lung cancer group, the mean MN/500 CB binucleated cells was 18.4 +/- 4.2, in the group with COPD, it was 8.3 +/- 4.1 with 8 patients having MN in the cancer range, i.e. 12-17. The mean MN/500 CB binucleated cells in the control group was 5.4 +/- 2.5. These differences were statistically significant. All cases with lung cancer and 63.9% of cases with COPD had a mean MN frequency greater than 95% CI of the mean MN frequency for the control group. Applying logistic regression analysis for the effect of risk factors revealed that lung cancer patients, who were current or ex- smokers, had significantly higher MN frequencies than patients with COPD

Genetic determinants of essential hypertension

This study aimed at determining the role of genetic and environmental risk factors in the development of essential hypertension in Alexandria, Egypt. A case-control-study was conducted in the Main Health Insurance Hospital [MHI] Alexandria, Egypt, whereby cases previously diagnosed as hypertensive were included in the study. A hospital-based control group visiting the hospital for other unrelated conditions and randomly selected in the same day as cases was also included in the study. Both cases and controls were subjected to a semi-structured questionnaire including information concerning socio-demographic data and risk factors for hypertension. Only cases were subjected to segregation analysis. This study included 165 cases with history of essential hypertension and 196 controls. Multivariate analysis of potential risk factors showed that the following factors are independently associated with an increased risk of essential hypertension; age over 40 years, elevated BMI, workers, ever smoker and stress. Education less than 6 years remained in the model as an independent protective effect. Segregation analysis proved that the disease is not inherited as single gene mode of inheritance. On the other hand, the heritability for 1st 2nd and 3rd degree relative was 28.2%, 28.7% and 20.0%. These figures provide evidence to multifactorial mode of inheritance in essential hypertension

Chromosome damage in passive smoker female

Current epidemiological data associates passive smoking with health hazards which not only affects the passive smoker but also affects the offsprings of passive smoker females. To determine the effect of cigarette smoke on the chromosomes of passive smoker females who were still in the childbearing age, the micronucleus [MN] frequency in 20 passive smoker females [spouse smoker] who had been exposed to cigarette smoke for at least 5 years was compared to the MN frequency in 20 control subjects [females with non-smoking spouse] all in the age group 31-39 years. The MN frequency among passive smoker female group ranged from 16-27 MN/500 cytokinesis blocked [CB] binucleated cell, with a mean of 21.1 +/- 3.7, while the MN frequency among the control group ranged from 3-11 MN/500 CB binucleated cell, with a mean of 8 +/- 1.7. The difference is statistically significant [t=14.2, p<0.01]. Applying the correlation coefficient test between age and MN frequency, a weak positive though non significant correlation was found between age and MN frequency in the passive smoker female group [R=0.11, p=0.630] while an intermediate positive but still non significant correlation was found between age and MN frequency in the control [R=0.26, p=0.27]. There was a positive correlation between the duration of exposure to cigarette smoke and the MN frequency, but this was statistically non significant [R=0.33, p=0.125]. The results emphasize that mothers especially in the childbearing age should not be exposed to cigarette smoke to avoid its deleterious effects on their health thus preventing any harmful effect the smoke can have on their offsprings

Relationship between head circumference and psychomotor development in down syndrome

In the present study, the head circumference of 44 Down syndrome patients as well as 80 control subjects was measured and plotted on the Egyptian control chart. Assessment of the psychomotor skills of Down syndrome patients and the control group was performed using the Denver development screening test. The developmental quotient was calculated. The head circumference of DS patients was significantly lower than the control group. The head circumference of Down syndrome patients showed deviation from the normal population range with advancing age. The gross motor sector showed the most severe delay in all ages studied. The language sector showed a decline with age and was the most retarded domain in the older Down syndrome patients. An intermediate +ve, though insignificant correlation, was found between the head circumference and the developmental quotient in Down syndrome patients aged 6 months - 1.5 years, while a strong +ve correlation between the head circumference and the developmental quotient was found in Down syndrome patients aged 1.5 - 2.5 years, implying that the head circumference plays a role in the psychomotor retardation of Down syndrome patients

Autosomal chromosome aberrations among children with severe mental retardation

Over a 4 year period, 240 children with severe mental retardation were evaluated cytogenetically. Their ages ranged from 2-11 years. Peripheral blood cultures were performed using the microtechnique. Chromosome examination was done using G-banding technique. Cytogenetic studies identified 63 [26.25%] cases with abnormal karyotypes including 55. Down syndrome; 51 standard and 4 translocated Down syndrome, 1 trisomy 18, 11 cases had structural autosomal aberrations; 10 unbalanced and 1 balanced, 4 had autosomal deletion, 2 had extrachromosomal material. The study revealed the need for an increased awareness to order chromosome analysis in those individuals with severe mental retardation

Cytogenetic findings in moderate and severe mental handicapped males

The aim of the present study was to estimate the frequency of various chromosomal abnormalities among the mentally handicapped males. A cytogenetic study done for 300 males with mental handicap, attending the Genetic Clinic, Medical Research Institute, Alexandria University, from institutions of the mentally retarded in Alexandria. 71 males [23.7%] has an abnormal karyotypes, 48 [16.0%] had Down syndrome, one [0.3%] had autosomal non-Down syndrome, 7 [2.3%] had structural autosomal aberrations other than Down syndrome [5 unbalanced, 2 balanced], 13 [4.3%] had fragile X-chromosome while, 2 [0.7%] had sex chromosome abnormalities. Chromosomal aberrations are important cause of mental handicap