Phenotypic variability in patients with isodicentric Y [p11.3]. Aclinical, cytogenetic and molecular study

Isodicentric [idic] chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. The prediction of their phenotypic consequences is often difficult because of the variety of genomic sequences concerned by duplications and deletions, and the variable degrees of mosaicism, 45, X cell line in particular, in various tissues. This study was conducted to provide more information on patients with idic [Yq] allowing a better phenotype-karyotype correlation and understanding the sexual differentiation in these patients. The study included 14 patients referred to the out patient clinic of the Human Genetics Department, Medical Research Institute, University of Alexandria. The reason for referral was genital ambiguity [8 patients], short stature with variable Turner stigmata [4 patients] and primary amenorrhea with normal height [2 patients]. All patients were subjected to clinical examination and chromosome analysis by GTG and CTG-banding techniques. Fluorescence in situ hybridization [FISH] and polymerase chain reaction [PCR] were done to determine the structure of the marker chromosomes detected by conventional methods. Chromosome analysis revealed a 45, X/46, X, idic [Y] [p11.3] in ten patients with variable degree of mosaicism, non mosaic 46, X, idic [Y] [p11.3] in two patients and a predominant 46, XX cell line along with 47, XX, idic [Y] [p11.3] cell line in two other patients .While the patients with an idic [Yq] described in this report were phenotypically different, all are considered as being at increased risk for gonadoblastoma. The great phenotypic variations seen in patients with an isodicentric Y chromosome greatly limit the genotype - phenotype correlation

Risk factors for hypospadias: a case control study

Despite being one of the most common congenital defects in boys, the etiology of hypospadias remains largely unknown. In this study we evaluated a spectrum of potential risk factors for hypospadias in which we focused on both paternal and maternal factors and chromosomal aberrations. Cases were selected from the Genetic Clinic, Medical Research Institute, University of Alexandria. A total of 176 cases with hypospadias were included in this study, and a matching control group ofnormal 300 boys for the association study. All cases were subjected to detailed family, pregnancy, genetic histories, clinical examination, and pedigree study. Chromosome analysis was performed using peripheral blood lymphocyte cultures by trypsin G-banding technique. Hormonal assays, abdominal and pelvic ultrasound were carried out according to case presentation. Both parents of cases and the control group completed written questionnaires. Abnormal karyotyes were detected in 23 cases [13.07%] associated with other anomalies, sex chromosome abnormalities were present in 69.56% and autosomal aberrations in 30.43%. Patients with chromosomal abnormalities were excluded from the association study. Logistic regression analysis was used to assess the independent contribution of different factors to the risk of hypospadias. Our data did not support an association with increased parental age. The most profound result was the increased risk of hypospadias for boys with positive family history [n=23; OR=26.36; 95%Cl: 5.90-164.23]. Strong indications for an increased risk of hypospadias were also found with low birth weight [n=45; OR=1 3.47; 95%Cl=6.09-30.70], preterm birth [n=6; OR=1 2.20; 95%Cl=1.45-271.47], twin or triplet pregnancy [n=4; OR=8.03; 95%Cl=0.84-190.23], and when mothers had preeclampsia [n=16; OR=11.56; 95%Cl=3.11-50.77]. Associations with pregnancy achieved with fertility treatment, and mother used iron supplements were also found. In conclusion, routine karyotype screening permits the diagnosis of chromosomal anomalies especially in those with the most severe forms of hypospadias and additional anomalies. Several risk factors have been identified for hypospadias which support the idea that genetic predisposition, placental insufficiency, and substances that interfere with natural hormones before conception or during fetal development play a role in the etiology of hypospadias

Cytogenetic study of tuberculous patients before and after chemotherapy

Increased chromosomal aberrations [CA] is regarded as a biomarker of personal exposure to dangerous chemical agents. Cytogenetic analysis was performed on 40 tuberculous [TB] patients [before] and after receiving anti-TB drugs], to evaluate the possible genetic damage induced by Mycobacterium tuberculosis as well as by short term combined anti-TB drugs [pyrazinamide, rifampicin, INH and ethambutol]. For comparison, 40 controls were selected. The frequency of CA in both TB patients groups [before and after treatment] showed a significant increase as compared to controls. The mitotic index was significantly decreased in both TB patients groups. TB infection by itself as well as the short term combined anti-TB drugs had a chromosome damaging effect on human lymphocytes in vivo. These drugs should be used with caution. Alternative drug combinations that are equally efficient but less harmful to the genome have to be selected. Cytogenetic analysis for detection of cases with CA [i.e. susceptible for progression or victims of mycobacterial or drug effects] should be advised to all patients especially in the child bearing age