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

BRCA1 [l85 del AG] mutation among Egyptian breast cancer female patients

This study was conducted to estimate the frequency of BRCA1 [1 85delAG] mutation among Egyptian female patients with breast cancer. Forty selected female patients with breast cancer, 80 of their female relatives and 10 healthy females as a control group were included in this study. Result: The age of onset of breast cancer was below 40 years in 25 [62.5%] patients and above 40 years in 15 [37.5%] patients.There were significant differences among the patients regarding the age at menarche before 13 years [P=0.011, P<0.05], onset of breast cancer [P=0.000, P<0.001], parity [P=0.000, P<0.001], first delivery before 30 years of age [P=0.04, P<0.05], breast feeding [P=0.002, P<0.05], and positive family history [P=0.000, P<0.001]. The frequency of BRCA1 [1 85delAG] mutation was found among 10% of the patients group .Eight percent of patients with early onset below 40 years and 13.5% of patients with onset after 40 years were heterozygotes for the mutation. Three percent of patients with unilateral breast cancer, 40% of patients with bilateral breast cancer and 50% of patients with breast ovarian cancer were carrying the mutation. Our results indicated that breast ovarian cancer and bilateral breast cancer patients were likely to have BRCA1 [l85delAG] mutation than in unilateral breast cancer

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

Inborn errors of metabolism among suspected patients referred to the genetics clinic in Alexandria

One thousand patients referred to genetics clinic, Medical Research Institute, Alexandria, were subjected to biochemical genetic studies and clinical genetic examinations to estimate the frequency of inborn errors of metabolism [IEM]. It was found that 70 [7%] patients had EM. Of these, 34 [48.6%] had aminoacidopathies, 3 [4.3%] had galactosemia, and 33 [47.1%] had lysosomal storage disorders. Phenylketonuria wqs the most frequent IEM [37.2%]. The rate of consanguinity among parents of patients with EM was high [77.1%] with 58.6% first cousins. Positive family history of more than one affected child was detected in 22 [31.4%] families of the patients with EM. Detection of IEM is important because it may allow a specific treatment for the patients and proper genetic counseling for the family

Prothrombin G20210A mutation in women with preeclampsia in Alexandria

The etiology and pathogenesis of preeclampsia remain unknown but it has been proposed that genetic predisposition to coagulation abnormalities contributes to the development of preeclampsia by increasing the thrombotic tendency. This study was conducted to estimate one of the thrombosis variant, prothrombin G20210A mutation, as a risk factor for preeclampsia. One hundred and seventeen preeclamptic women and 102 normal control group were included in this study, both groups were in the 3[rd] trimester of pregnancy. A positive association was found between maternal age over 35 years [OR = 8; Cl: 1.54-44.23], previous preeclampsia [OR = 6.34; Cl: 2.16-19.96], positive family history of hypertension [OR 3.44; Cl: 1.28-9.60], diabetes mellitus [OR = 10.14; Cl: 1.24-221.181, history of recurrent abortions [OR = 24.05; Cl: 1.39-416.94], intrauterine fetal death [OR = 19.50; Cl: 1.11-342.65], and fetal anomalies [OR 8.42; Cl: 1.06-180.0] and preeclampsia. The frequency of heterozygous carriers of the prothrombin G20210A mutation in preeclamptic women [6.8%] was higher than that in controls [2.9%], but the difference was statistically non-significant. However, the frequency of prothrombin mutation was statistically higher in severe preeclamptic women [14.7%] compared to women with mild preeclampisa [3.6%] [P<0.05]. This indicated that prothrombin mutation is associated with severe preeclampsia and worsens the prognosis of the disease

Newborn screening for certain treatable inborn errors of metabolism in Alexandria

As outlined in the Newborn Screening Task Force report published in August 2000, the newborn screening system is more than the just testing, but also involves follow up, diagnosis, treatment, and evaluation. Newborn screening is aimed at early detection and intervention of treatable inborn errors of metabolism and also at establishing the incidence of these disorders. Specimens of dried blood spots were collected from infants born in Alexandria, attending 13 Health Offices in different Districts of Alexandria for BCG vaccination, and the tests were done in the Human Genetics Department, Medical Research Institute, Alexandria University. The total number screened was 3000 infants, of them; one [0.033%] infant had hyperphenylalaninemia, one [0.033%] infant had classic galactosemia and 11 [0.37%] infants had high level of thyroid stimulating hormone [TSH], on confirmatory test, 9 of them were found to be euthyroid

Hereditary persistence of fetal hemoglobin and genetic heterogeneity in Alexandria, Egypt

Fetal hemoglobin [HbF] production in normal adults varies over a 20-fold range and is under genetic control. To estimate and assess the mode of inheritance of hereditary persistence of fetal hemoglobin [HPFH], 1009 apparently healthy preparatory school students were included in this study. Fetal hemoglobin and other hematological indices were determined in these subjects. Four hundred and twenty four subjects had HbF representing 42.4%. The levels of HbF ranged from 0.4%-39.5%. The frequency distribution of HbF showed 2 groups, low [9.5% for F1, > 5% for F2]. The hemoglobin [Hb] content showed a positive correlation with HbF level which may indicate the increased HbF in mildly anemic adults. Mathematics of population genetic on families of 66 subjects with elevated HbF showed that autosomal dominant inheritance was the possible mode in 18 families [X[2] = 9.68]. In other families, the value of heritability for the first degree relatives was 91% suggesting the multifactorial inheritance. In conclusion, this form of HPFH is heterogenous and the mode of inheritance is different in different families