MOLECULAR ANALYSIS OF ANDROGEN RESISTANCE SYNDROMES IN EGYPTIAN PATIENTS

Androgen resistance syndromes [i.e. 5 alpha-reductase deficiency (5 al pha RD) and androgen receptor (AR) defects] are frequently reported am ong Egyptian intersex patients. This study examined AR and Sa-reductas e 2 (5 alpha R2) gene mutations among a sample of such cases as a firs t step towards instituting a screening program. Five families with a t ypical hormonal profile of 5 alpha RD were screened for major deletion s of exons 3-5 of the 5 alpha R2 gene, using polymerase chain reaction (PCR) and electrophoresis. Thereafter, screening for point mutations was carried out by single strand conformational polymorphism (SSCP) an alysis, followed by nucleotide sequencing Seven patients with androgen insensitivity syndrome (AIS) were subjected to molecular analysis of AR exons B-H by a similar protocol, except for the use of denaturing g radient gel electrophoresis (DGGE) for screening point mutations. No m ajor deletions were found in either gene. One family had abnormal elec trophoretic mobility on SSCP of exon 5 of the 5 alpha R2 gene, resulti ng from a point mutation (C to T substitution) at codon 246. Another f amily, showing retarded mobility on DGGE, had a point mutation (G to A substitution) at codon 889 of the AR gene. In conclusion the study re vealed two mutations previously reported in other geographically disti nct populations, inferring the possibility of mutational hot spots in the genes.