ESPE Abstracts

Background: A 8-year-old Chinese girl was referred by the endocrinologist of our hospital because of ambiguous external genitalia.Physical examination revealed breast and axillary hair and pubic hair at Tanner stage 1, There had two mass located within two side of inguinal regions,labia fusion, the size of clitoris was 2.0×1.0 cm, there was a vaginal opening. US images revealed a solid nodile suggestive of testicular tissue located in both inguinal regions. The MRI exam confirmed a testicle in the deep inguinal ring on both sides. The uterus and Fallopian tubes were absent.The blind-ended vagina length was 4.0 cm. The baseline testosterone (T) and dihydrotestosterone (DHT) and androstenedione (△4A)concentration were 0 nmol/l, 0.51 ng/ml, 21.66 pg/ml respectiverly, After the HCG stimulation test, T and DHT and (Δ4A concentration were 4.69 nmol/l, 0.628 ng/ml, 99.88 pg/ml respectiverly. The T/DHT ratio was 14.2, The T/Δ4A ratio was 2.4. Her karyotype was a normal 46, XY complement.

Objective and hypotheses: The aim of the study was to verify the mutation of the AR gene to molecular cause of this patient of 46, XY DSD.

Method: DNA was extracted from peripheral leukocytes and all exons of the AR genes were amplified by PCR. The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in patient and his parents. Amino-acid substitutions were studied in silico to predict the effects using Polyohen2 and SIFT software

Results: A c.1685 T>C mutation (p.Ile562Thr) on exon 2 of the AR gene was identified in the patient. But the locus mutation of the AR gene had never been reported was found in the one thousand – genome database dbSNP database and BGI internal database.The structure prediction of the mutated protein was significantiy changed. All three in silico algorithms predicted affected protein function with a conserved amino acid throughout species (Polyohen2: probably damaging with a 0.99 score; SIFT :damaging with a 0.0 score; Mutation Taster: disease causing). By verifying the site of patients parents, the mother carried the same mutation, The father was found to be normal, which is consistent with an x-linked patter of AIS.

Conclusion: A c.1685 T>C mutation (p.Ile562Thr) on exon 2 of the AR gene could result in androgen insensitivity syndrome.