Molecular characterization of X chromosome fragility in idiopathic mental retardation

Background: Fragile X syndrome [FXS] is the most common form of inherited mental retardation. Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients is relatively high. Cytogenetic diagnosis of FXS is unreliable since it is ineffective for the diagnosis of premutated males or females. Proper molecular diagnosis is a pre-requisite for providing proper counseling advice

Subjects and methods: Sixty-four males with idiopathic mental retardation, ranging in age from 4.2 to 19 years [10.92+/- 4.00] were clinically pre-selected, based on scoring protocol comprising eight features of the syndrome, before molecular testing. A rapid polymerase chain reactionbased screening was applied for detection of expanded FMR1 alleles. Samples that did not yield the normal band lengths were subjected to a second PCR screen. The secondary screen utilizes a chimeric primer demonstrating the presence or absence of an expanded allele

Results: Amplification of FMRI gene by PCR of tested patients revealed that 8 cases [12.5%] have full mutation and 6 cases [9.4%] have premutation. A wide range of Fra X-scoring ranging from 1 to 7 features was detected in examined cases. Significant clinical features included large prominent ears, hyperextensibility of joints and macroorchidism in post pubertal males

Conclusions: A simplified checklist of fragile X should be used for patients with idiopathic MR and those patients above score 3 should be tested for FXS. The diagnostic assay may be used as a screening method for fragile X syndrome being rapid and cost effective compared to other techniques. In addition, screening of all relatives of proven patients should be performed to detect clinically unidentified cases for provision of proper counseling and optimal management of detected cases

Genetic study of congenital limb anomalies among Egyptian children

This study has been conducted to reveal genetically-determined factors that underlie the development of congenital limb anoma1…m9ng a sample of Egyptian infants and children. These data might prove useful' in taking preventive measures and/or providing proper counseling to concerned families. The study comprised studying 140 [One hundred and forty] Egyptian children with congenital limb anomalies. They consisted of [98] males and [42] females ranging in age from 10 days to 18 years. All cases were selected from among patients attending the outpatient medical genetics clinic, faculty of medicine, Ain-Shams university, Cairo-Egypt. Enrolled cases were subjected to a list of investigations including complete history with pedigree construction, anthropometric measurements and full clinical examination. In addition, specific radio-imaging studies and laboratory investigations were done for cases necessitating further diagnostic workup. The results of the study revealed that isolated limb anomalies were found in [55] patients representing [39.3%] of cases. The remaining eighty five [85] patients constituting [60.7%] of enrolled cases comprised two groups: those with limb defects as part of a well defined genetic syndrome [Syndromic limb defects] [76 patients-54.3%] and those with limb defects as part of a chromosomal aberration syndrome [9 patients-6.4%]. Genealogical data of the study revealed that parental consanguinity is found in [47.3%] of cases with isolated limb defects, in [72.3%] of cases with syndromic limb defects and in [44.4%] of cases with limb defects due to chromosomal abnormalities. Valid history of prenatal drug intake by the mother was found in [43.6%] of cases with isolated limb defects, in [25%] of syndromic limb defects and in none of the cases with chromosomal abnormalities. Detailed analysis of data of the study drew useful recommendations regarding many aspects like the possibility of prenatal diagnosis of most cases as well as the availability of many curative and/or palliative intervention measures for early detected and managed cases. Of prime importance, however, is the urgent need of alerting gynecologists and obstetricians taking care of pregnant women to the important role played by iatrogenic prescription of drugs during pregnancy in causation of many types of congenital limb anomalies. Cessation of this non-based evidence medical attitude is necessary and can result in a significant reduction in drug-induced congenital limb anomalies among newbornsmedical attitude is necessary and can result in a significant reduction in drug-induced congenital limb anomalies among newborns

Gene analysis and carrier detection of Duchenne muscle dystrophy in Egyptian families

Duchenne and Becker muscular dystrophy [D/BMD] are X-linked recessive disorders resulting from mutations in the DMD gene. Since there is no cure or effective treatment for progressive muscular dystrophy, prevention of the disease is important and strongly depends on carrier status in-formation. Two-thirds of DMD/BMD cases are familial, thus female relatives are candidates for carrier-risk assessment. Segregation analysis of polymorphic short tandem [CA]n repeats [STR-[CA]n] was used to establish and compare the haplotypes of DMD patients with those of their at-risk relatives in order to determine the carrier status. However, 59 D/BMD index families and 35 of their at-risk female relatives were analyzed using the ion-pair reversed phase high performance liquid chromatography [IP-RP-HPLC] method. Comparison between the results of CPK of the carriers and linkage analysis revealed that values higher than the normal level were compatible in 100% of the cases with the carrier status. On the other hand, normal values do not distinguish between the healthy and carrier populations. In conclusion, the unlabeled IP-RP-HPLC-STR assay represents an excellent molecular tool for carrier-status identification and consequently the genetic counseling for the early prevention of such diseases

Mast cell-mediated angiogenesis in chronic venous leg ulcers

The male patients, aged 30-55 years, of chronic venous leg ulcers and 10 healthy controls of the same age were studied for angiogenesis and mast cell changes. The surface area [SA] of the newly formed thin walled capillary vessels were counted, using counting graticule, in relation to skin SA. All patients exhibited angiogenesis. The mast cells were greatly increased [57954/mm3] and this increase was highly significant [P <0.01], and their activities were marked