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

Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density in postmenopausal Egyptian women

Low bone mineral density is a major risk factor for development of osteoporosis. The estrogen receptor alpha gene is a candidate locus for genetic influence on bone mass. The possible association between two polymorphisms in the first intron of this gene, independently or in combination, and bone mineral density was widely studied in different population. In the present study, the relationship of TC [Pvull] and AG [Xbal] polymorphisms to variability in bone mineral density [BMD] was determined in 69 unrelated postmenopausal Egyptian women aged 43-75 years. All of the participants were non-smoker with no history of medication affecting bone loss or bone turnover. Hepatic and renal investigations were evaluated to ensure normal functions. BMD at the calcaneous bone was measured by peripheral computed tomography and expressed as t-values for the corresponding age. Analysis of the TC [Pvull] and AG [Xbal] polymorphisms revealed that BMD was significantly lower in women with homozygous absence of the restriction sites, in other words, women with the PP genotype showed significant reduction in their bone mass than in those with the pp genotype. And women with the XX genotype showed significant lowered BMD compared to those with Xx then xx genotypes. Analysis of combined genotypes in the same sample revealed that BMD was significantly lower in Egyptian women with the PPXX genotype [ANOVA, P= 0.002] than in those with the PpXx genotype [ANOVA, P= 0.022]. The xxpp genotype did not exhibit any significance association with the reduced BMD in either the osteoporotic or osteopenic groups. The overall distribution of ER Pvull and Xbal genotypes frequency identified in the present study: Pp 55%, pp 20%, PP 17%, Xx 55%, xx 30%, XX 10% is consistent with that found in the postmenopausal American white women, and postmenopausal Italian women, as the heterozygous [ +/- ] Pvull or Xbal genotype is the most prevalent one then the homozygous presence of restriction site, [+/+] genotype, followed by the homozygous absence of the restriction sites, [-/-] genotype is the least prevalent one. Identified allele frequencies [P= 0.52, p= 0.48 and X= 0.42, x= 0.58] at the two polymorphisms are in Hardy-Weinberg equilibrium. Results of the present analysis, which to the best of our knowledge is the first one in our population, suggest that testing for ER Pvull and Xbal restriction fragment length polymorphisms might be useful in screening and identifying postmenopausal Egyptian women at risk for developing osteoporosis, PPXX followed by PpXx genotypes were found to be associated with reduction in BMD in our population

C677T polymorphism of the 5,10-Methylenetetra-hydrofolate reductase [MTHFR] gene as a risk factor for neural tube defects among Egyptian families

Methylenetetrahydrofolate reductase [MTHFR] deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects [NTDs]. C677T MTHFR polymorphism is associated with NTDs, in some populations. Although the prevalence of this mutation has been reported from various ethnic populations, no data concerning Egyptian are available. C677T polymorphism was analyzed by PCR-RFLP. The frequencies of the C677T MTHFR polymorphism was determined in 35 case mothers, 19 case fathers and 9 children with NTDs compared with healthy 30 matched controls. In addition, allele and genotype frequencies were classified into different groups according to offspring NTD phenotype, consanguinity of the parents and number of affected offspring with NTD and or abortion. The prevalence of the polymorphic, homozygous [T/T] and heterozygous [C/T] C677T MTHFR genotypes were 6.3% and 38.1%, respectively, giving an allele frequency of 0.25. We observed increased frequency of heterozygotes of MTHFR in NTDs mothers versus the control although, C677T allele frequency was 0.28 in controls. Consanguinity rate was 45.7% among our families but it seems unlikely that it had an additional effect on the heterozygosity of the mutant genotype in this sample. In conclusion, neither homozygosity nor heterozygosity for the C677T polymorphism in the MTHFR gene constitute a genetic risk factor in the total NTDs but could be a risk of spina bifida aperta in this sample of Egyptian families. It is noteworthy to mention that this is the first report from Egypt evaluating the relationship between MTHFR677C>T and NTD

Molecular diagnosis of spinal muscular atrophy in Egyptians

This study was carried out with 33 spinal muscular atrophy [SMA] patients. DNA molecular studies of the SMA gene on the long arm of chromosome 5 [5q11.2q13.3] revealed homozygous deletion of exon 7 in 55% of cases, 36% of whom also had a homozygous delition of exon 8. The adult patients were heterozygous for an abnormal size exon 8. The remaining patients had either compound heterozygote deletion of exons 7 and 8 or were normal for both. There may therefore be 5q-unlinked SMA or SMA due to other mutations. Detection of deletions of SMA exons 7 and 8 is a powerful diagnostic test in patients with SMA, but other mutations among Egyptians must also be sought