Molecular analysis of androgen resistance syndromes in Egyptian patients

• Published in: Disease markers Vol. 13; no. 2; pp. 99 - 105
• Main Authors: ESSAWI, M, GAD, Y. Z, EL-ROUBY, O, TEMTAMY, S. A, SABOUR, Y. A, EL-AWADY, M. K
• Format: Journal Article
• Language: English
• Published: Amsterdam IOS Press 01.04.1997; Oxford; Berlin
• Subjects: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - deficiency; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics; Biological and medical sciences; Disorders of Sex Development - diagnosis; Disorders of Sex Development - etiology; Disorders of Sex Development - genetics; Egypt; Electrophoresis, Polyacrylamide Gel; Exons; Genetic Testing; Gynecology. Andrology. Obstetrics; Humans; Male; Male and female genital diseases. Gonadal dysgenesis. Hermaphroditism. Sex hormones resistance; Medical sciences; Point Mutation; Polymorphism, Single-Stranded Conformational; Receptors, Androgen - deficiency; Receptors, Androgen - genetics; Sequence Analysis, DNA; Sequence Deletion; Syndrome; Tropical medicine; Africa; Egypt; Endocrinopathy; Human; Androgen; Congenital disease; Male pseudohermaphroditism; Case study; Polymerase chain reaction; Resistance; Malformation; Deletion; Mutation; Molecular biology; Sex steroid hormone; Male genital diseases
• ISSN: 0278-0240; 1875-8630

Androgen resistance syndromes [i.e. 5 alpha-reductase deficiency (5 alpha RD) and androgen receptor (AR) defects] are frequently reported among Egyptian intersex patients. This study examined AR and 5 alpha-reductase 2 (5 alpha R2) gene mutations among a sample of such cases as a first step towards instituting a screening program. Five families with a typical hormonal profile of 5 alpha RD were screened for major deletions 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) analysis, 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 gradient gel electrophoresis (DGGE) for screening point mutations. No major deletions were found in either gene. One family had abnormal electrophoretic mobility on SSCP of exon 5 of the 5 alpha R2 gene, resulting from a point mutation (C to T substitution) at codon 246. Another family, showing retarded mobility on DGGE, had a point mutation (G to A substitution) at codon 889 of the AR gene. In conclusion, the study revealed two mutations previously reported in other geographically distinct populations, inferring the possibility of mutational hot spots in the genes.