1/40. An androgen receptor mutation in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core is associated with complete androgen insensitivity.Subjects with androgen insensitivity syndromes (AIS) are characterized by a 46, XY karyotype, presence of testes, normal or elevated androgen levels in blood, and impairment of the usual response to androgens associated with various aberrations of male differentiation and virilization ranging from slightly undervirilized men to phenotypic females. Here we describe a novel proline to serine mutation in codon 892 (exon 8) of the androgen receptor in a patient with complete androgen insensitivity. The mutation is located in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core. Investigation of androgen binding in cultured testicular fibroblasts of the patient revealed a reduced AR binding capacity (11 fmol/mg protein) and a highly elevated Kd value (3.1 nM) in comparison to control genital skin fibroblasts. Cotransfection studies with an androgen-responsive reporter gene revealed a diminished transactivation property of the mutant androgen receptor.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
2/40. Embryonic testicular regression syndrome: a case report.A case of testicular regression syndrome was reported. The patient was an 18 year old girl presenting with primary amenorrhoea. physical examination revealed normal female external genitalia and underdeveloped secondary sexual characteristics. Hormonal profile indicated gonadal failure. Chromosome analysis revealed 46,XY karyotype. Diagnostic laparoscopy demonstrated undeveloped internal genital organs. Remnants of epididymis, vas deferens and seminiferous tubule were uncovered during exploratory laparotomy. Ontogeny of sexual differentiation and pathogenesis of testicular regression syndrome were reviewed and discussed.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
3/40. Complete androgen insensitivity in a 47,XXY patient with uniparental disomy for the x chromosome.We describe a unique patient with complete androgen insensitivity syndrome and a 47,XXY karyotype. Androgen receptor assay using cultured pubic skin fibroblasts showed no androgen-binding capacity. sequence analysis of the androgen receptor gene demonstrated two nonsense mutations, one in exon D and one in exon E. Microsatellite marker analysis showed that the patient is homozygous for all five Xq loci examined. The results suggest that the long-arms of the two X chromosomes are identical, i.e., uniparental isodisomy at least for Xq, and carry the same mutations in the androgen receptor gene. This explains how complete androgen insensitivity syndrome occurred in this 47,XXY individual.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
4/40. 46, XY female--a case report.INTRODUCTION: We examine a presumptive case of complete androgen insensitivity syndrome (CAIS) with certain unusual features. CLINICAL PICTURE: A woman with early onset osteoporosis gave a history of primary amenorrhoea and surgery for intraabdominal gonads. She subsequently defaulted follow-up and hormone replacement therapy. Endocrinological evaluation revealed hypergonadotrophic hypogonadism associated with a 46,XY karyotype. TREATMENT: Therapy included reinforcement of the female phenotype and oestrogen replacement. OUTCOME: There was gradual development of her secondary sexual characteristics and improvement in her bone mineral density. CONCLUSION: patients with CAIS need proper counselling and education according to their psychosexual make-up and sociocultural factors. The importance of long-term oestrogen replacement in a young subject post-gonadectomy cannot be overemphasized as illustrated in our case.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
5/40. Characterization of a novel receptor mutation A-->T at exon 4 in complete androgen insensitivity syndrome and a carrier sibling via bidirectional polymorphism sequence analysis.The complete androgen insensitivity syndrome (AIS) is a sub-type of X-linked male pseudohermaphroditism resulting from total dysfunction of the androgen receptor. Affected patients are phenotypically female despite a 46,XY genotype; gonadal tissue displays a classic Sertoli cell-only pattern on microscopic examination. We describe the diagnosis and management of a 19(1/2)-year-old patient who presented for primary amenorrhea and absent cervix, identified incidentally during a routine Pap test. serum total testosterone was elevated (725 ng/dl) and the karyotype was 46,XY. Molecular investigation for specific gene defect(s) causing disruption and functional incapacity of the androgen receptor was undertaken for the proband and her only sibling. From this we discovered a previously unknown hemizygous mutation (A-->T) in exon 4 of the androgen receptor gene, associated with replacement of asparagine (AAT) with tyrosine (TAT) in the resultant androgen receptor protein [N705Y]. Bidirectional, non-isotopic sequence analysis of exon 4 was next undertaken for the proband's sister who was found to be heterozygous for this mutation. Psychological and genetic counseling was provided to both individuals; the patient underwent an outpatient laparoscopic orchiectomy without complication. She continues to receive oral hormone replacement therapy following an oral contraceptive model. In this report, the clinical approach to AIS is outlined from a reproductive endocrinology perspective with special emphasis on psychological counseling and laboratory methods employed to confirm the diagnosis at the molecular level. We also outline other recently described mutations of the androgen receptor gene (Xq11-12) which have been associated with AIS.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
6/40. Antenatal diagnosis and early laparoscopic treatment of a rare variation of androgen-insensitivity syndrome.androgen-insensitivity syndrome (AIS) (Testicular feminisation or Morris syndrome) is characterised by external female genitalia and bilateral testes with a normal male karyotype. This kind of syndrome is transmitted recessively. Presence of hypoplastic and short "pseudo-vagina" is one of the characteristics of this syndrome. We report here a case of AIS in which there was a well-formed vagina (6 cm). The case was diagnosed antenatally and managed laparoscopically.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
7/40. A 19 year old with complete androgen insensitivity syndrome and juvenile fibroadenoma of the breast.We report a case of a 19-year-old female with complete androgen insensitivity syndrome (CAIS) who was diagnosed with a juvenile fibdroadenoma of the breast. The patient presented at age 18 with primary amenorrhea. She had been raised as a female and went through thelarche at age 13 and adrenarche at age 14. She had two sisters and three maternal aunts with androgen insensitivity syndrome. Physical exam revealed that the patient had no cervix, and a pelvic sonogram confirmed that the uterus was absent. Genetic analysis revealed a 46 XY karyotype. Bilateral intra-abdominal testes were noted on ultrasound and subsequently removed. She was placed on synthetic estrogen replacement therapy. Roughly 1 year following orchiectomy, the patient noticed an enlarging mass in her right breast. Physical exam revealed a roughly 5 cm mobile mass in the upper portion of the nipple-areolar complex. Ultrasound showed a solid mass consistent with a fibroadenoma. Because of the size of the lesion and the patient's hormonal make-up, a fine needle aspirate was obtained. Cytopathology showed large cohesive sheets of ductal epithelial cells, scattered histiocytes, numerous bare nuclei, fragments of fibrous tissue and metachromatic stroma. Some of the stroma was noted to be cellular. The tumor was subsequently excised. Microscopically, the lesion had epithelial and stromal hyperplasia consistent with a fibroadenoma. Phyllodes-like qualities of large size, increased stromal cellularity, and intracanalicular growth ("leaf-like projections") were noted; however, the pathologist found that the florid epithelial hyperplasia and the patient's young age were more compatible with a juvenile fibroadenoma. We describe what we believe to be the first report of a patient with CAIS and a fibroadenoma of the breast. The hormonal imbalance typically found in these patients, combined with the fact that most individuals with CAIS receive exogenous estrogen therapy, suggests that there may be a relatively high incidence of fibroadenoma in these patients.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
8/40. A novel point mutation of the androgen receptor (F804L) in an Egyptian newborn with complete androgen insensitivity associated with congenital glaucoma and hypertrophic pyloric stenosis.androgen-insensitivity syndrome (AIS) is a major cause of male pseudohermaphroditism (MPH). Although AIS is usually reported as a monogenic disease resulting from androgen receptor (AR) mutations, on rare occasions it has been observed as part of a multiple congenital anomaly syndrome. We report here a patient who was the first newborn girl of an unrelated couple. Shortly after birth, the diagnoses of congenital glaucoma and pyloric stenosis were made. A detailed history of the father's family revealed that nine members presented glaucoma before 40 years of age. Clinical and ultrasound evaluation showed two inguinal testes, with female external genitalia and no Mullerian derivatives. The patient had a 46,XY karyotype, good testicular response to gonadotrophin stimulation and a remarkably high T : dihydrotestosterone ratio. Sequencing of the five exons of the 5alpha-reductase type 2 gene (SRD5A2) was normal. Conversely, a de novo point mutation was found in exon 6 of the AR gene, resulting in an F804L substitution, which has never been described previously. To our knowledge, the association of complete AIS, congenital glaucoma and pyloric stenosis has also never been reported previously.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
9/40. A novel point mutation in the hormone binding domain of the androgen receptor associated with partial and minimal androgen insensitivity syndrome.Mutations in the coding sequence of the androgen receptor (AR) gene result in a wide range of androgen insensitivity syndromes (AIS). We report an extended family in which at least five male individuals in different generations suffer from partial AIS. The index patient presented at birth with ambiguous genitalia; the karyotype was 46,XY and subsequent sex assignment male. Elevated stimulated testosterone (T) and normal baseline gonadotropins were found. family history revealed four additional adult males affected with various abnormalities of their external genitalia. Molecular analysis of the coding sequence of the AR gene revealed in all a novel point mutation in exon 6, changing threonine to isoleucine at codon position 800 in the hormone-binding domain. We conclude that phenotypic variations in mild AR defects are striking and can remain undetected even until late in life.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
10/40. Complete androgen insensitivity syndrome due to X chromosome inversion: a clinical report.We have studied a patient with complete androgen insensitivity syndrome (CAIS) and a 46, inv(X),Y karyotype. The patient's mother and maternal aunt also carry the inverted X, and the mother is phenotypically normal, with a 46, inv(X),X karyotype, while a maternal aunt has CAIS with a 46,inv(X),Y karyotype. Molecular cytogenetic studies demonstrate that one of the X inversion breakpoints occurs within Xq11.2-12, which is the locus for the androgen receptor. FISH analysis demonstrated that a BAC clone containing the androgen receptor gene was disrupted by the inversion. We therefore hypothesize that disruption of the androgen receptor gene causes CAIS in this patient. This is the first report of CAIS caused by a chromosome inversion.- - - - - - - - - - ranking = 3keywords = karyotype (Clic here for more details about this article) |
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