ABSTRACT
Androgen insensitivity syndrome (AIS) is a X-linked disorder of sexual differentiation resulting from defective androgen receptor (AR) function. Androgens are secreted by the testes of 46,XY individuals, but there is loss of target organ response to the hormone. The abnormalities of AR are due to defects in the AR gene, and many mutations causing AIS have been reported since the cloning of AR gene. In this study, we analyzed the AR genes in twelve Korean patients with androgen insensitivity syndrome: 9 patients with complete AIS and 3 patients with partial AIS DNAs were isolated from patients with AIS, and the coding region of AR gene was amplified by a polymerase chain reaction using 7 pairs of primers (exon B-H). Sequence analysis of the AR gene was performed using direct sequencing and single strand conformational polymorphism (SSCP). The AR gene mutations were identified in 7 out of 12 patients: 6 of 9 patients with complete AIS, and one of 3 patients with partial AIS. Mutations found were as follows: the point mutation (ATT->ACT) at position 680 of exon D, point mutation (TGG->TGC) at position 751 of exon E, point mutation (CAA->TAA) at position 792 of exon F, point mutations (CGC->TGC, GTG->ATG) at position 855 and 866 of exon G, and the deletion of 13 nucleotides (CGTATCATTGCAT) at position 840 of exon G, respectively. To the best of our knowledge, the point mutations found in exon D, exon E, and exon F, and the deletion in exon G have not been observed before. SSCP revealed bands with abnormal mobility in 10 out of 12 patients tested. Mutations were found 5 out of these 10 patients. The other two patients showed no abnormal band on SSCP, but showed mutations by direct sequencing. In conclusion, we have demonstrated the AR gene mutations, including three novel mutations, in Korean patients with AIS, and these abnormalities might be related to the pathogenesis of androgen insensitivity syndrome.
Subject(s)
Humans , Male , Androgen-Insensitivity Syndrome , Androgens , Clinical Coding , Clone Cells , Cloning, Organism , DNA , Exons , Nucleotides , Point Mutation , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Receptors, Androgen , Sequence Analysis , Sex Differentiation , TestisABSTRACT
OBJECTIVE: To investigate the clinical significance of endometrial thickness and pattan as a predictor of successful implantation of embryos in ovum donation and cryopreserved-thawed embryo transfer program. METHODS: From January, 1996 to March, 1998, 31 cycles of ovum donation and 31 cycles of cryopreserved-thawed embryo transfer were enrolled in this prospective study. Endometrial thickness was measured three times: prior to progesterone administration (P), 1 day and 3 days after P. In cryopreserved-thawed embryo transfer cycles, the measurement at 1 day after P was omitted. Endometrial pattern was observed prior to progesterone, and was considered meaningful when a multi-layered triple-line was seen with prominent outer and central hyperchogenic lines and inner hypoechogenic regions. RESULTS: There were no differences in embryo quality, dose or duration of estrogen, and endometrial thickness or pattern between conception and non-conception cycles in both ovum donation and cryapreserved-thawed embryo transfer pmgram. In ovum donation cycles, no cortelation was observed between estrogen dose and endometrial thickness or pattern. In cryopreserved-thawed embryo transfer cycles, total estrogen dose and endometral thickness at 3 days after P has a inverse correlation, and estrogen dose over 4.3 mg per day can predict expression of a multi-layered triple-line pattern, CONCLUSION: Endometrial thickness or pattern. cannot predict a successful implantaion of embryos in both ovum donation and cryopreserved-thawed embryo transfer cycles.