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

Detection of chromosome 22q11 micro deletions among children with isolated congenital heart disease using PCR

Congenital heart disease [CHD] is the most common form of human birth defects, affecting 0.4% to 0.9% of all live-born neonates. It is the leading non-infectious cause of mortality in newborns. Nowadays echocardiogram plays an important role on the diagnosis. This procedure is able to identify a wide range of malformations. However, despite the advances in diagnosis and treatment of congenital heart malformations, our understanding of the causative mechanisms has been limited. Previous studies suggest that a substantial number of patients with CHD have a 22q11 deletion. The type of CHD observed is variable, but frequently there is involvement of the conotruncal anomalies. Chromosome 22q11 deletion syndrome can be inherited in an autosomal dominant fashion or result from a de novo deletion or translocation. Therefore, early diagnosis of this syndrome is important both for management of the patient and for assessing risk of recurrence in future pregnancies. The objectives of this study were to determine the frequency of chromosome 22q11 deletions in patients with isolated CHD, and to compare between this prevalence among different groups of CHD. We studied a series of 75 children with CHD [proven by detailed echocardiography] attending the cardiology unit in El-Shatby pediatrics university hospital. After taking the parents consent, each patient was subjected to complete genetic assessment. Of 75 patients approached, 15 were found affected with well recognized genetic syndromes, and, therefore, excluded from the study. We analyzed the 60 patients with' apparently' isolated CHD for 22q11 microdeletions by PCR assay using three highly polymorphic microsatellite markers [D22S941, D22S944 and D22S264]. The results proved that VSD was the most common type of CHD. Cardiac phenotypes were classified into 2 groups: conotruncal anomalies [5/60], and non- conotruncal anomalies [55/60]. Chromosome 22q11 deletions were identified only in three patients. The prevalence of 22q11 microdeletion in different groups of CHD was: 20% [1/5] among the group of conotruncal anomalies, and 3.6% [2/55] among those with non-conotruncal anomalies. The 22q11 microdeletions are more prevalent among patients of the conotruncal group. There fore, it is recommended that patients with CHD of conotruncal type should undergo 22q11 microdeletion testing so genetic counseling can be offered as well as proper diagnosis management of associated manifestations

Frequency of Arg[972]-IRS-1 variant among type I diabetic patients in El-Shatby pediatric Hospital, Alexandria, Egypt

Several polymorphisms have been identified in the amino acid sequence of human insulin receptor substrate-1 [IRS-1]. The most prevalent one is glycine change to arginine at the codon 972 that was hypothesized to play a role in pancreatic beta-cell stimulus-coupled-insulin secretion and survival. The frequency of this variant among type I diabetic patients, their available normal sibs, and control subjects recruited from EI-Shatby Pediatric Hospital, Alexandria University were studied. The results showed that the frequency of Arg[972] IRS-1 variant was 14% in diabetic patients, 9.1% in normal sibs, and 4% in normal control subjects. Data revealed that Odds ratio showed that carriers of Arg[972] IRS-1 variant had four times increased risk for developing the disease. In sibs, the risk is increased by three fold in carriers of this variant as compared to sibs with the wild allele. In spite being non-significant, the results of the present work suggest that Arg[972] IRS-1 variant could be considered as a potential risk factor for developing type I diabetes although it was statistically non-significant, which may be attributed to the small sample size or methods of selection of cases

Genetic study of multiple congenital contractures [Arthrogryposis Multiplex Congenita]

This work was carried out to study different conditions with arthrogryposis and their mode of inheritance that would allow proper diagnosis, management and appropriate genetic counseling. The study included 30 patients with arthrogryposis attending the Genetic Clinic, Medical Research Institute, Alexandria University. The frequency of parental consanguinity was 50%. An abnormal pregnancy history was found in 22 cases. Both upper and lower limb affections were noticed in twenty-eight patients, while isolated upper limb affection occurred in one case and isolated lower limb affection in one case. Finger joints were the most commonly affected. It was concluded that the examination of all joints in the upper and lower limbs is the key of diagnosis in the majority of cases of arthrogryposis. There is a marked inter- and intra-familial variability in many conditions with arthrogryposis. An accurate diagnosis is important in genetic counseling, prevention, management and prognosis