Testicular feminization syndrome and associated gonadal tumors in Denmark

Bangsbøll, Susanne; Qvist, I.; Lebech, P. E.; Lewinsky, Marianne

doi:10.3109/00016349209007950

Cited by 115 publications

(38 citation statements)

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“…In Denmark, b was reported to be 2 Â 10 À5 , and this is probably an underestimate because not all cases, especially of complete insensitivity (CAIS), have been ascertained [Bangsboll et al, 1992]. CAIS, which is caused by complete loss-offunction mutations, is observed in B50% of cases [Bangsboll et al, 1992;Gottlieb et al, 1999].…”

Section: Ar Androgen Insensitivity Syndrome (Ais)mentioning

confidence: 99%

Direct estimates of human per nucleotide mutation rates at 20 loci causing mendelian diseases

2002

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Communicated by Steve S. Sommer I estimate per nucleotide rates of spontaneous mutations of different kinds in humans directly from the data on per locus mutation rates and on sequences of de novo nonsense nucleotide substitutions, deletions, insertions, and complex events at eight loci causing autosomal dominant diseases and 12 loci causing X-linked diseases. The results are in good agreement with indirect estimates, obtained by comparison of orthologous human and chimpanzee pseudogenes. The average direct estimate of the combined rate of all mutations is 1.8 Â 10 À8 per nucleotide per generation, and the coefficient of variation of this rate across the 20 loci is 0.53. Single nucleotide substitutions are B25 times more common than all other mutations, deletions are Bthree times more common than insertions, complex mutations are very rare, and CpG context increases substitution rates by an order of magnitude. There is only a moderate tendency for loci with high per locus mutation rates to also have higher per nucleotide substitution rates, and per nucleotide rates of deletions and insertions are statistically independent on the per locus mutation rate. Rates of different kinds of mutations are strongly correlated across loci. Mutational hot spots with per nucleotide rates above 5 Â 10 À7 make only a minor contribution to human mutation. In the next decade, direct measurements will produce a rather precise, quantitative description of human spontaneous mutation at the DNA level. Hum Mutat 21:12-27,

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Section: Ar Androgen Insensitivity Syndrome (Ais)mentioning

confidence: 99%

Direct estimates of human per nucleotide mutation rates at 20 loci causing mendelian diseases

2002

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“…2,8 Interestingly, the occurrence of intratubular germ cell neoplasia in pediatric patients, which is at a maximum of 6% of cases, does not reach the frequency of germ cell cancer in adulthood reported in most literature. 2,[8][9][10][11] The prevalence of intratubular germ cell neoplasia appears to be remarkably higher (15%) in pediatric patients with partial androgen insensitivity than in patients with complete androgen insensitivity. 4 Hannema et al described that residual activity of AR has a positive effect on the development of Wolffian structures and the enlargement of seminiferous tubules during puberty in patients with complete androgen insensitivity syndrome.…”

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confidence: 99%

Complete androgen insensitivity syndrome: factors influencing gonadal histology including germ cell pathology

et al. 2014

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Patients with complete androgen insensitivity syndrome are at an increased risk for the development of gonadal germ cell cancer. Residual androgen receptor (AR) activity and abnormal gonadal location may influence the survival of atypical germ cells and the development of other histopathological features. To assess this, we evaluated 37 gonads from 19 patients with complete androgen insensitivity (ranging in age from 3 months to 18 years). Histological abnormalities were examined using hematoxylin and eosin-stained sections and sections stained for POU5F1 and KITLG, markers of early changes in germ cells at risk for malignant transformation. Hamartomatous nodules (HNs), Leydig cell hyperplasia (LCH), decreased germ cells, tubular atrophy and stromal fibrosis were more pronounced as age increased (Po0.001). Expected residual AR activity acted as a positive predictor only for non-malignant germ cell survival in (post)pubertal patients (Po0.05). Immunohistochemical studies indicated that delayed maturation of germ cells was present in three patients, whereas intermediate changes that occurred between delayed maturation and intratubular germ cell neoplasia, designated pre-intratubular germ cell neoplasia, were identified in four cases. Intratubular germ cell neoplasia was observed in one patient. Neither POU5F1 nor KITLG expression was dependent on expected residual AR activity. An independent effect of inguinal versus abdominal position of the gonads was difficult to assess because inguinal gonads were present primarily in the youngest individuals. In conclusion, many histological changes occur increasingly with age. Expected residual AR activity contributes to better survival of the general germ cell population in (post)pubertal age; however, it did not seem to have an important role in the survival of the germ cells at risk for malignant transformation (defined by POU5F1 positivity and KITLG overexpression) in complete androgen insensitivity. Comparison of the high percentage of patients in our study that were carrying germ cells with delayed maturation or pre-intratubular germ cell neoplasia with previously reported cumulative risk of tumor development in adult patients indicates that not all such precursor lesions in complete androgen insensitivity will progress to invasive germ cell cancer.

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“…We have investigated sexual function in a cohort of women with complete androgen insensitivity syndrome (CAIS), an intersex condition with an estimated incidence of between 1 in 13,158 to 40,800 live births (3,4). Complete androgen insensitivity syndrome occurs early in XY fetal development when the androgen receptors completely fail to function, leading to the birth of a female infant.…”

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confidence: 99%