Clinical, anthropometric, radiological and molecular characteristics of Egyptian achondroplasia patients

Achondroplasia is the most common form of non lethal skeletal dysphasia. It is a fully penetrant autosomal dominant disorder and the majority of cases are sporadic resulting from de novo mutations associated with advanced paternal age. The phenotype of achondroplasia is related to disturbance in endochondral bone formation due to mutations in the fibroblast growth factor receptor-3 [FGFR3] gene. Evaluation of the cardinal phenotypic features in achondroplasia, the body physique using anthropometric measurements, the characteristic radiological signs in the patients as a main tool for diagnosis and detection of the most common mutations in achondroplasia patients in the studied sample. From 42 cases referred to us as achondroplasia, we selected 20 cases where clinical manifestations were consistent with achondroplasia. Cases were subjected to full clinical examination, detailed anthropometric measurements, whole body skeletal survey and molecular studies of the most common mutations of the FGFR3 gene using PCR amplification technique. Nineteen cases were sporadic [95%] and one case had an affected father [5%]. A paternal age above 35 years at the time of child's birth was present in 7 cases [35%]. Paternal exposure to occupational heat was noted in 6 cases [30%] and parental exposure to chemicals in 3 cases [15%]. All cases showed typical clinical and radiological manifestations of achondroplasia. Anthropometric measurements quantitatively confirmed the body physique in the studied eases. G380R common mutations of the FGFR3 gene were detected in 15/18 cases [83%] with the G to A transition at nucleotide 1138 in 14 cases [77%]. Agenesis of corpus callosum, not previously reported in association with achondroplasia, was present in the only case with the G-C transversion mutation at nucleotide 1138 [5%]. Awareness of the cardinal features of achondroplasia, proper anthropometric measurements and detailed skeletal survey are the key for accurate diagnosis, genetic counseling and avoidance of over diagnosis. The majority of studied Egyptian achondroplasia patients have the same common mutation that has been most often defined in patients with achondroplasia from other countries

Molecular characterization of 21 hydroxylase deficiency congenital adrenal hyperplasia in Egyptian children: a pilot study

Defective steroid synthesis due to derangements of 21-hydroxylase gene [CYP21] constitutes the most frequent cause of congenital adrenal hyperplasia [CAH] and is one of the most frequent inborn errors of metabolism world wide. The molecular basis of CYP21 mutations is complicated. During meiosis gene conversion occurs and transfers deleterious point mutations from the inactive [CYP21P] to the corresponding sequence of the CYP21 gene causing either complete or partial inactivation of 21-hydroxylase activity. Allele specific polymerase chain reaction [ASPCR] was used for the detection of the 4 most common mutations in CYP21 gene: Intron 2 splice mutations [IVS2-13], 8bp deletion in exon 3 [del-8bp], I172N mutation in exon 4 and V281L mutation in exon 7, in 11 salt wasting SW-CAH Egyptian infants. In the examined 22 alleles, 2 alleles were carrying del-8bp, 3 were carrying IVS2-13 mutation, 4 with I172N, 4 with V281L. In the present study the percentage of undetectable mutations was 50%. The wide range of genetic mutations reported for CYP21 gene reconfirm the marked heterogeneity of the disorder among Egyptian and calls for more extensive molecular work

Longitudinal study for prediction of type 1 diabetes in siblings of patients: an initial step for prevention of disease

The aim of this study was identification of cut off points of positivity of different antibodies [Ab] against islet cell antigens [ICA, Anti GAD Ab, Anti IA2 Ab] in Egyptian children and adolescents who are sibs of patients with type 1 diabetes as well as determination of their insulin secretory capacity and identification of HLA-DQB1 alleles known to predispose to or protected against type 1 diabetes. The ultimate aim is to identify those at high-risk of the disease to enroll them in preventive trials. This study was a longitudinal one that lasted for five years and include seventy-two sibs of type 1 diabetic patients recruited from the Diabetic Endocrine Metabolic Pediatric Unit [DEMPU] at Cairo University Children's Hospital. Thirty sex healthy subjects; age and sex matched with patients and with negative family history of autoimmune diseases were included as controls. Serum samples from all subjects and controls were analyzed for GAD[65], IA2 Ab using radioimmunoassay and ICA Ab using ELISA technique. Sibs who were positive for one or more Ab were further subjected to the assessment of first phase insulin response and HLA studies for detecting DQB1 alleles known to predispose or protect against type 1diabetes using SSP DNA-based technique. The results showed that 36 sibs [50%] were GADAb positive, 10 sibs [13.9%] were IA2 Ab positive while 14 sibs [19.4%] were ICA positive with overlap. Mean FPIR in 41 sibs positive for one or multiple Ab was 41.407 mU/L +/- 28.73 which was statistically significantly less than that in controls 79.414 mUL +/- 44.316 [P<0.001]. Thirty-four sibs [38%] lied in the high-risk group defined by FPIR less than 5[th] percentile. HLA studies done in 32 sibs showed that 17/32 sibs [54.84%] had the predisposing alleles DQB1 [0201, 0202, 0302, 0303, 0401] while 7 sibs [22.28%] had protective alleles DQB1 [0301, 0601]. Prevention of type 1diabetes will require reliable methods for early diagnosis of predisposition to the disease, using improved genetic and serological screening on a side scale and identification of the primary antigenic target[s] for specific tolerance. Those at risk [multiple positive antibodies and reduced insulin secretory response] in absence of HLA protective alleles are to be enrolled in preventive trials