Genetic evaluation of proportionate short stature in Alexandria, Egypt

Compared with a genetically relevant population, short stature [ss] is defined as a standing height more than 2 standard deviations below the mean [or below the third percentile] for gender. SS is a common problem for children and adolescents worldwide. This study was conducted to reveal the spectrum of the genetic causes of proportionate ss in Alexandria, Egypt. A total of 120 patients with proportionate SS, [87 girls and 33 males], ages ranging from 6 months to 15 years, selected from the Human Genetic Clinic, Medical Research Institute, Alexandria University, Egypt, were included in this study. All patients were subjected to detailed genetic and family history, clinical genetic examination with particular attention to body proportions and dysmorphic features, anthropometric measurments, radiological examination and chromosomal analysis. Parental consanguinity was found among 60.4% of the patients. About 37.5% of the cases had positive family history of short stature. It was found that proportionate SS was due to pathologic causes in 87.5% of the cases and to normal growth variants as constitutional growth delay and familial short stature in 12.5% of the cases. Pathologic causes included fetal malformation syndromes [27.2%], genetically determined systemic diseases [23.3%], chromosomal abnormalities [20%], and endocrine disorders [17.6%]. About 25% of the studied girls had Turner syndrome. Accurate diagnosis of SS modifies the management plan for the patient and allows psychological and genetic counseling for the family. Karyotype analysis is recommended for all girls with unexplained SS. A sensitive screening system and an effective referral channel to genetic centers are especially important in the management of SS

molecular study of methylenetetrahyrofolate reductase gene in mothers of standard down syndrome patients

The observation that a lot of children with Down syndrome are born to mothers with young age made it important to identify the mechanisms involved in this young age group. It was found that DNA hypomethylation is associated with chromosomal instability and abnormal chromosome segregation. This knowledge led to the clarification of the role of enzymes involving in the methylation reaction like Methylene Tetrahydrofolate Reductase enzyme [MTHFR]. The C-T common polymorphism at nucleotide 677 [C677T], which results into an alanine to valine substitution in the MTHFR protein, caused higher thermolability and reduced enzyme activity in lymphocyte extracts. In order to verify this association, we studied the presence of the C677T polymorphism of the MTHFR gene in 50 mothers of Down syndrome children and 50 control mothers. A non-significant higher incidence of the mutant T allele in Down syndrome children mothers [6%] than in control [2%] was detected. These results do not support the presence of an increased risk of Down syndrome mothers carriers of the T allele in Egyptian population