ESPE Abstracts (2016) 86 P-P2-418

Phenotype, Genotype and Gender Identity in Pubertal and Post-Pubertal Patients with Androgen Insensitivity Syndrome

Iram Shabir, Madan Khurana, Angela Joseph, Marumudi Eunice, Manju Mehta & Ariachery Ammini


All India Institute of Medical Sciences, New Delhi, India


Background: Androgen insensitivity syndrome (AIS) is a rare disease due to end organ resistance of androgens. AIS is commonly caused by the mutations of androgen receptor (AR) gene located on chromosome Xq11-12. The mode of inheritance is hemizygous, where males get severely affected and females remain as carriers.

Objective and hypotheses: Here, we describe the Phenotype–Genotype correlation and gender identity of pubertal and post pubertal patients with AIS.

Method: Records of patients attending the endocrine clinic of our tertiary care hospital and new patients with diagnosis of AIS were compiled. All patients had detailed history, physical examination, chromosomal analysis and hormonal studies done. Chromosomal analysis was carried out on G-banded metaphases obtained from 72-h cultures from peripheral blood. The genotype of the patients was analysed for AR and SRD5A2 gene mutations. LH, FSH, T were estimated by Electrochemiluminiscence using commercially available kits from Roche, Germany. DHT and androstenedione (A) were extracted from plasma by diethyl ether and separated from other androgens by Celite-chromatography and estimated by radioimmunoassay (Immunotech, DSL9600i, Czech Republic, Prague). DNA was isolated from the blood samples, quantified and subjected to PCR amplification using specific primers for AR and SRD5A2 gene.

Results: Clinical diagnosis of AIS was established in 32 patients. Out of these, 20 patients presented in pubertal and post-pubertal age group (10–20 years). The mean age of presentation was 18.3±4.5 years and the present age of the patients was 19.2±4.3 years. 12 patients (60%) sought medical attention with the complaint of primary amenorrhoea and were initially reared as females. Gender (re) assignment was done in three patients and nine patient continued as female. All patients had normal 46, XY karyotype. Mean LH was 20.9±11.3 mIU/ml, FSH was 9.7±5.7 mIU/ml, Testo was 8.45±5.0 ng/ml, DHT was 746.8±449.4 pg/ml, T/DHT was 10.0±5.8, A was 1.85±0.95 ng/ml and T/A was 5.13±3.8. The molecular analysis of AR gene showed the presence of mutant alleles in 15 patients. We found two novel mutations p.T105R and p.P133A in exon 1. One patient had an inherited hemizygous AR mutation along with the de novo homozygous mutation in the SRD5A2 gene. No mutation was present in five clinically established patients with PAIS.Among these five children, four were initially reared as female and two had male gender re-assigned during childhood. None of them had gender dysphoria.

Conclusion: No specific genotype–phenotype correlation could not be established in our patients but confirming the diagnosis of AIS with assessment of AR and SRD5A2 gene may help in better management.

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