Klinefelter's syndrome, mosaic 46,XX/46,XY/47,XXY/48,XXXY/48,XXYY: a case report

A 35-year-old male was investigated for primary infertility. Clinical examination showed an intelligent man with normal facial appearance and moustache and small firm testes. Testicular histopathology revealed marked atrophy of the testes with no spermatogenesis and absence of germ cells. Hormonal profile showed elevated levels of FSH,LH and low levels of testosterone. Chromosome analysis from whole blood culture showed cells with 46,XX/46,XY/47,XXY/48,XXXY/48,XXYY mosaicism. The predominant cell line was 47,XXY (87.86%). 46,XY/47,XXY mosaicism is not uncommon. However, mosaicism of multiple sex chromosome aneuploidy is rarely observed. This is the first report of mosaicism in Klinefelter's syndrome variant with five cell lines.     

Multiple pterygium syndrome in five Arab sibs

This report describes an Arab family in which the parents are first cousins and with 5 siblings having multiple pterygium syndrome. The last pregnancy which produced an affected sib was prenatally diagnosed by ultrasonography. Intrafamilial variability of clinical features is discussed. The report stresses the importance of the differentiation between various genetic entities with multiple pterygium.     

YAP‐TEAD signaling promotes basal cell carcinoma development via a c‐JUN/AP1 axis

The mammalian Hippo signaling pathway, through its effectors YAP and TAZ, coerces epithelial progenitor cell expansion for appropriate tissue development or regeneration upon damage. Its ability to drive rapid tissue growth explains why many oncogenic events frequently exploit this pathway to promote cancer phenotypes. Indeed, several tumor types including basal cell carcinoma (BCC) show genetic aberrations in the Hippo (or YAP/TAZ) regulators. Here, we uncover that while YAP is dispensable for homeostatic epidermal regeneration, it is required for BCC development. Our clonal analyses further demonstrate that the few emerging Yap‐null dysplasia have lower fitness and thus are diminished as they progress to invasive BCC. Mechanistically, YAP depletion in BCC tumors leads to effective impairment of the JNK‐JUN signaling, a well‐established tumor‐driving cascade. Importantly, in this context, YAP does not influence canonical Wnt or Hedgehog signaling. Overall, we reveal Hippo signaling as an independent promoter of BCC pathogenesis and thereby a viable target for drug‐resistant BCC.     

A direct synthetic approach to uracil anhydrothionucleoside derivatives

Direct conversion of peracylated N¹-(β-d-glucopyranosyl)-2-thiouracil derivatives into the corresponding anhydrothionucleosides has been studied under various conditions including: gas-phase pyrolysis, heating without a solvent, and by heating in a solvent of high boiling point (DPE) in the presence of a base (DABCO) and reaction in a microwave reactor. Heating at 210-220 °C was found to give the best yield of a single isomer. The structures of the new anhydrothionucleosides were confirmed by NMR techniques.     

Studies on Bacillus stearothermophilus. Part 1. Transformation of progesterone to a new metabolite 9,10-seco-4-pregnene-3,9,20-trione.

When Bacillus stearothermophilus, a thermophilic bacterium isolated from the Kuwaiti desert, was incubated with exogenous progesterone for 24 h, three monohydroxylated metabolites were produced. 20-Hydroxyprogesterone was the major metabolite produced in 60.8 relative percentage yield. The other two monohydroxylated metabolites were identified as 6β-hydroxyprogesterone and the rare 6-hydroxyprogesterone in 21.0 and 13.6 relative percentage yields, respectively. A new metabolite 9,10-seco-4-pregnene-3,9,20-trione was isolated in 3.7 relative percentage yield. All metabolites were purified by preparative TLC and HPLC followed by their identification using ¹H, ¹³C NMR and other spectroscopic data.     

Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal muscular atrophy

Two genes are known to be involved in spinal muscular atrophy (SMA), namely, SMN (survival motor neuron) and NAIP (neuronal apoptosis inhibitory protein). Deletion analysis of these genes has been reported for many ethnic groups. We have extended this analysis to include 15 Arabic patients (11 unrelated cases of type I, which represent practically all of the patients diagnosed within the last 2 years in Kuwait, and 4 type-II cases from a single kinship). Also, 41 healthy relatives (parents and sibs) and 44 control individuals of Arabic origin were analyzed. The homozygous deletions of exons 7 and 8 of the SMN gene were found in all SMA patients studied. Exon 5 of NAIP was homozygously absent in all type-I patients, but was retained in type-II cases. Among members of SMA families, one mother was found to be homozygously deleted for NAIP. All of the control individuals had both normal SMN and NAIP. Our results are in agreement with the general consensus that the incidence of NAIP deletion is higher in the more severe SMA cases. Furthermore, they suggest that SMA type-I chromosomes, with the dual deletion of the SMN and NAIP genes, are more common in Arabs than in patients of other ethnic origin. Received: 23 April 1996 / Revised: 17 June 1996