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

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

Genetic study of patients with proportionate growth deficiency referred to human genetics clinic, in Alexandria

Growth deficiency is the term that describes a growth rate below the appropriate growth velocity for age. Normal stature varies widely among ethnic groups and within each ethnic group approximating a normal distribution. Short stature may be proportionate or disproportionate. Children with proportionate short stature may have more generalized disorders. The aim of the present work was to study the phenotypic variations in patients with proportionate growth deficiency, and to evaluate the diagnosis to provide accurate genetic counseling. The study included 53 patients with proportionate growth deficiency from those attending the Human Genetics Clinic, Medical Research Institute, Alexandria University, during a four years period. They were subjected to a complete genetic and family history, pedigree analysis, complete genetic examination, ant hropometric measurements, cytogentic analysis and others investigations when needed. The results showed that group I consisted of 17 cases [32.07%] with chromosomal anomalies [7 cases with numerical aberrations and 10 cases had structural anomalies], group II included 21 patients [39.62%] with single gene disorders [11 patient had autosomal dominant disorders. 9 cases with autosomal recessive diseases and only I case with X-linked recessive disorder]. Group Ill consisted of the sporadic syndromes [11 cases; 20.75%] and the last group had disorders due to teratogens [4 cases; 7.56%]. It is essential that a specific diagnosis should be made because there are hundreds of causes for growth deficiency that have differing prognoses, complications and responses to treatments

Mental retardation among children born with birth defects

Mental retardation [MB] is a major health problem affecting 3% of the population. It results from the interaction of many genes and non-genetic factors. However, in up to 60% of patients the aetiology remains unclear. The aim of the study is to examine the association of birth defects and MB, taking into consideration the type of birth detect, level of MB, co-occurrence of MB with other developmental disabilities, genetic and biological risk factors. A case control study was conducted on 300 children with MR from December 2006 to December 2007. They were referred to the Human Genetics Department, Medical Research Institute, University of Alexandria, for diagnosis and genetic counseling. For comparison, 506 normal control groups were randomly selected. The cases were 156 males [54%] and 135 females [46%], the difference was not statistically significant. Out of 300 studied cases, 72 children [24%] had various chromosomal aberrations, while the remaining 228 [76%] had single gene disorder. From these groups 66 children had another coexisting DDS [25 with CP, 15 had VL, 10 with autism; 10 HL and 6 had epilepsy]. Mild MB [MMR] was more prevalent among all the studied cases than severe MR [SMR], there was significant association between 8MB and birth defects [OR = 1.65, Cl: 1.05-3.27]. Birth defects occurred in 180 children [40 children with Down syndrome, 1 with sex chromosomal defect, 3 with other chromosomal anomalies, and the remaining 136 with non-chromosomal abnormalities]. There was significant association between children with Down syndrome and birth defects [OR=10; Cl: 1-242.25]. Birth defects were present in 41 children with MR and other coexisting DDs. Also, it was found that all children with different birth defects had significant association with MB, [OR = 87.21 Cl: 40.38-196.31]. These MR risks tended to be the largest among infants born with heart and central nervous system defects. There was significant association between low birth weight [OR = 3.57; Cl: 1.91-6.65], preterm [OR = 9.63; Cl: 2.21-47.84], and parental consanguinity [OR = 4.19; Cl: 2.9-6.06] and the occurrence of MR. This study high-lights the role of prenatal factors in the origin of many DDS especially MR and suggests that a sizable proportion of DDS may be caused by insults occurring early in embryologic development

Females with gonadal dysgenesis: cytogenetic and molecular analysis

Gonadal dysgenesis [GD] is a congenital defect in gonadal development related to abnormalities of genes controlling sexual differentiation and includes a wide spectrum of patients with variable phenotypes and chromosomal constitutions. This study aimed at studying the spectrum of chromosomal abnormalities as related to the phenotypic variability of GD cases and to detect the presence of Y-ctiromosome specific sequences in these patients by using molecular techniques in order to allow, early prophylactic management. Seventy females presenting with female GD were referred to the Human genetic clinic, National Research Center for cytogenetic analysis and genetic counseling. Patients were subjected to clinical examination, pedigree construction, cytogenetic and molecular analysis. Hormonal studies, pelvic ultrasonogrophy, Laparoscopy and gonadal biopsy were performed whenever possible. Patients were classified according to their Karyotypes into 9 groups. The most frequent Karyotype, was 45, X [34.3%]. The association of 45, X with other cell lines were found at a rate of 28.6%. The age of studied cases ranged between 15 days to 31.07 years [mean=14:0.9 years]. The total parental consanguinity rate reached 44.3%. Gonadal dysgenesis and short stature are the two cardinal signs in these patients. Skeletal features were detected among all studied groups with highest scores in patients having complete X monosomy [44.6%]. Neck webbing was a characteristic sign of patients with non-mosaic 45, X karyotype. Dysmorphic features were detected in all groups with the exception of groups with 46, XX and 46, XY Karyotypes. Hirsutism and other virilizing signs were not commonly detected among the studied cases. Gonadoblastoma was detected in only one case among the 5 cases examined by Laparoscopic biopsy. Unidentified sex chromosomes markers constituted 35% of all our 45, X mosaic patterns. Molecular analysis of the markers using PCR technique proved the presence of Y specific sequences, SRY, in three cases. The over all rate of Y chromosomal material detected among these patients either by cytogenetic or molecular methods was 14, 3%

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

Risk Factors [genetic and environmental] associated with isolated congenital malformations in Alexandria, Egypt

Congenital malformations [CM] affect 2-3% of all births and are the leading causes of perinatal deaths and also infant mortality and morbidity. Both genetic and environmental factors can cause birth defects. This study aimed at accurate diagnosis to detect the frequency of different types of the CM and evaluating the risk factors [genetic and environmental] implicated in developing these anomalies. A case-control study was conducted on 522 cases during the period from June 2001 to June 2003. For comparison, 506 normal control group was randomly selected. The frequency of isolated cases was 31.03% [162/522 cases]. The highest frequency of CM involved the Urogenital systems [56.2%], followed in descending order by Central Nervous System [14.8%], Eye anomalies [13%], Congenital Heart Disease [9.3%], Cleft lip and/or palate [4.9%] and Gastro-intestinal anomalies [1.8%]. There was a significant association between neonatal risk factors as male sex [OR = 2.77; Cl: 1.85-4.19], low birth weight [OR = 4.53; Cl: 2.60-7.92], and preterm [OR = 6.82; Cl: 2.68-18.73] and the occurrence of CM. Other risk factors as twinning did not have a significant influence on the frequency of CM, while breech presentation had a significant protective effect from CM. There was a positive association between the maternal risk factors as young maternal age [<25 years; OR = 1.53; Cl: 1.03-2.27], positive consanguinity [OR = 4.63; Cl: 3.13-6.85], repeated abortion [OR = 6.59; Cl: 2.83-16.19] and CM. Maternal exposure to drugs such as female sex hormones, antibiotics, and analgesics, as well as maternal illness during the 1st trimester of pregnancy, had a significant effect on the frequency of CM. Although, pre-eclamapsia, oligohydramnios, and polyhydramnios are known to be complicated with CM, this study could not verify this association. The study emphasizes that determination of etiology of CM is an important step towards primary prevention

Genetics of congential malformations of the central nervous system

This study was conducted on one hundred and four patients with the aim of studying the genetics of CNS malformations as well as determining the relation between CNS malformations and inbreeding. Microcephaly was present in forty-five patients of which thirty-seven had single gene defects, seven had a chromosomal abnormality, while one patient was born to a diabetic mother. Neural tube defects [NTD] were present in thirty-two patients, whereas macrocephaly was present in eleven patients. Congenital hydrocephaly was present in nine patients, while holoprosencephaly [HPE] was present in seven patients. The frequency of consanguineous mating among parents of children with CNS malformations was 48.1%, this value was significantly higher than that of the general population. Parental consanguinity was significantly higher in patients with microcephaly, macrocephaly and congenital hydrocephaly. The average inbreeding coefficient in patients with CNS malformations was double that of the Egyptian population. It was especially elevated in patients with microcephaly, macrocephaly and hydrocephaly reflecting increased homozygosity