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

Anophthalmia/microphthalmia: clinical, ophthalmological and imaging findings

This study described the craniofacial anomalies in correlation with ocular, intracranial, cytogenetic and electro- physiological findings in children with anophthalmia/microphthalmia. Twenty cases with congenital anophthalmia/microphthalmia [11 males, 9 females with age range from 8 days to 9.5 years] were examined. Seventeen cases had bilateral clinical anophthalmia/microphthalmia, while three cases had unilateral microphthalmia/anophthalmia. Patients with clinical anophthalmos/microphthalmia had associated congenital brain malformations [10/20 patients, 50%], genital anomalies [6/20, 30%] and major congenital orodental abnormalities [2/18 patients, 11.1%]. Eight cases of 11 with bilateral microphthalmia [72.7%] were reported to have bilateral congenital cataract. In addition, 6 cases [6/10, 60%] had abnormal visual evoked potentials [VEP] and electroretinogram [ERG]. The results presented the correlation between VEP and clinical, neuroimaging picture and/or the ophthalmological abnormalities. Eye defects are heterogeneous, since they were observed in clinical patterns with all modes of inheritance. Autosomal-recessive syndromes represent 55% of total syndromes, followed by syndromes of autosomal-dominant inheritance [15%], X- linked dominant [10%], chromosomal structural abnormalities [10%] and caused by environmental agents [10%]. Nevertheless, high rate of consanguinity [11 cases, 55%] with mean inbreeding coefficient of 0.0512 and the similarly affected sibs highlight the role of single gene disorder in the country. The contribution of electrophysiology of the eye, MRI of brain, cytogenetic and orodental examinations were useful for better determination of visual function and identification of potential underlying multisystem disease, subsequently, improving parental understanding and genetic counseling