(33/226) Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?

We investigated whether molecular defects in the CYP21 gene were detectable in two common sex chromosome aberrations, the Turner and the Klinefelter syndromes. We found abnormal 17-hydroxyprogesterone levels after adrenal stimulation in 26/60 (43.3%) patients affected by these chromosome aberrations, as compared with only 11/68 (16.2%) normal controls (P=0.0014, odds ratio 4.0). Screening of the CYP21 gene identified a single Val281Leu missense mutation in exon 7 in 9/63 (14.3%) of the patients, all nine of whom were heterozygote carriers; the mutation frequency was significantly higher than in the general population (P=0.007, odds ratio=3.5). The hormonal and molecular data indicate that these common sex chromosome aberrations are associated with a remarkably high frequency of steroidogenic defects. It may be hypothesised that reduced levels of steroid 21-hydroxylase could confer a survival advantage, leading to a successful pregnancy.  (+info)

(34/226) Birth of a healthy male after frozen thawed blastocyst transfer following intracytoplasmic injection of frozen thawed testicular spermatozoa from a man with nonmosaic Klinefelter's syndrome.

We here report on a birth of a male, with normal karyotype, after frozen thawed blastocyst transfer following intracytoplasmic injection of frozen thawed testicular spermatozoa from an azoospermic 27-year-old man with nonmosaic Klinerfelter's syndrome. Testicular sperm were retrieved by percutaneous needle biopsy.  (+info)

(35/226) Multiple endocrine disorders and Rathke's cleft cyst with Klinefelter's syndrome: a case report.

A 46-year-old Japanese male was admitted for the evaluation of severe hypertension. He was obese and had a eunuchoidal body habitus. Chromosomal analysis revealed a 46, XY/47, XXY karyotype. Serum LH, FSH and testosterone levels were low, indicating hypogonadotropic hypogonadism. Endocrinological dynamic tests disclosed presence of hypothalamic panhypopituitarism, partial diabetes insipidus, type 2 diabetes mellitus and low renin essential hypertension. Brain computed tomography and magnetic resonance imaging revealed intra- and extrasellar masses. Histological examination of the tissue obtained at transsphenoidal surgery showed a Rathke's cleft cyst (RCC). To the best of our knowledge, this is the first case report of mosaic Klinefelter's syndrome accompanied by symptomatic RCC, type 2 diabetes mellitus and low renin essential hypertension.  (+info)

(36/226) Diabetes mellitus associated with Klinefelter's syndrome: a case report and review in Japan.

We report a case of Klinefelter's syndrome in a 48-year-old man who had diabetes mellitus associated with severe insulin resistance. We diagnosed him with Klinefelter's syndrome from his atrophic testicles, primary hypogonadism in hormonal examination, and a chromosomal aberration of 47,XXY. He showed severe decreased insulin sensitivity in a hyper-insulinemic euglycemic clamp test. He had injected over 100 units of insulin per day, however, testosterone replacement and administration of pioglitazone improved his glycemic control, which resulted in a decrease of insulin dose to less than 50 units per day. Here, we discuss the characteristics of diabetes mellitus associated with Klinefelter's syndrome in Japanese patients including this case.  (+info)

(37/226) Unbalanced X;autosome translocations provide evidence for sequence specificity in the association of XIST RNA with chromatin.

Whether XIST RNA is indifferent to the sequence content of the chromosome is fundamental to understanding its mechanism of chromosomal inactivation. Transgenic Xist RNA appears to associate with and inactivate an entire autosome. However, the behavior of XIST RNA on naturally occurring human X;autosome translocations has not been thoroughly investigated. Here, the relationship of human XIST RNA to autosomal chromatin is investigated in cells from two patients carrying X;autosome translocations in the context of almost complete trisomy for the involved autosome. Since trisomies of either 14 or 9 are lethal in early development, the lack of serious phenotypic consequences of the trisomy demonstrates that the translocated autosomes had been inactivated. Surprisingly, our analyses show that in primary fibroblasts from adult patients, XIST RNA does not associate with most of the involved autosome even though the bulk of it exhibits other hallmarks of inactivation beyond the region associated with XIST RNA. While results show that XIST RNA can associate with human autosomal chromatin to some degree, several observations indicate that this interaction may be unstable, with progressive loss over time. Thus, even where autosomal inactivation is selected for rather than against, there is a fundamental difference in the affinity of XIST RNA for autosomal versus X chromatin. Based on these results we propose that even autosomal chromatin that had been inactivated earlier in development may undergo a stepwise loss of inactivation hallmarks, beginning with XIST RNA. Hence compromised interaction with XIST RNA may be a primary cause of incomplete or unstable autosomal inactivation.  (+info)

(38/226) Testicular sonography in men with Klinefelter syndrome shows irregular echogenicity and blood flow of high resistance.

PURPOSE: Klinefelter syndrome is the most common chromosomal aberration among azoospermic men. We wanted to compare testicular echogenicity and intratesticular arterial blood in men with this syndrome versus men with normal sperm parameters. METHODS: Testicular sonography including Doppler imaging, was performed as part of the infertility workup in 26 men with Klinefelter syndrome as well as in 26 men with normal sperm parameters. RESULTS: In men with Klinefelter syndrome, sonography of the testicular parenchyma revealed a heterogeneous irregular pattern with spread hyper- and hypoechoic foci. Doppler sonography resulted in waveforms of high impedance patterns, reflecting intratesticular blood flow of a high resistance. In men with normal sperm parameters testicular echogenicity was of an almost homogeneous regular pattern. In these men, intratesticular blood flow typically exhibited a pattern of low vascular resistance. CONCLUSIONS: The study demonstrates that testicular echogenicity as well as intratesticular blood flow are different in men with Klinefelter syndrome versus men with normal sperm parameters.  (+info)

(39/226) Genetic diagnosis of Werdnig-Hoffmann disease: a problem for application to prenatal diagnosis.

We report a floppy infant with Werdnig-Hoffmann disease (spinal muscular atrophy: SMA type 1) and Klinefelter syndrome. After genetic counseling with parents, a genetic diagnosis using DNA from the infant's peripheral blood mononuclear cells was performed. The parents' deletion of exons 7 and 8 of the survival motor neuron (smn) gene and exons 4 and 5 of the neuronal apoptosis inhibitory protein (naip) gene were noted in the infant, so he was confirmed to have SMA type 1. The parents wanted to receive a prenatal diagnosis on the next pregnancy. However this genetic test is achieved by confirming that a specific band can not be detected by PCR. Therefore, this method should be applied with great care to prenatal diagnosis using chorionic villi, which may be contaminated with maternal tissue.  (+info)

(40/226) Aberrant recombination and the origin of Klinefelter syndrome.

Trisomy is the most commonly identified chromosome abnormality in humans, occurring in at least 4% of all clinically recognized pregnancies; it is the leading known cause of pregnancy loss and of mental retardation. Over the past decade, molecular studies have demonstrated that most human trisomies originate from errors at maternal meiosis I. However, Klinefelter syndrome is a notable exception, as nearly one-half of all cases derive from paternal non-disjunction. In this review, the data on the origin of sex chromosome trisomies are summarized, focusing on the 47,XXY condition. Additionally, the results of recent genetic mapping studies are reviewed that have led to the identification of the first molecular correlate of autosomal and sex chromosome non-disjunction; i.e. altered levels and positioning of meiotic recombinational events.  (+info)