Chromosome abnormalities in tuberous sclerosis

Summary In fibroblasts cultured from biopsies of the skin lesions of six patients with tuberous sclerosis (TS) there was a variable but consistent degree of karyotypic variation. Premature centromere disjunction (PCD) of all or part of the chromosomes, micronuclei, an increased incidence of breaks, dicentric chromosomes and the presence of polyploid metaphases were found in all cultures. The PCD was of the type encountered in Roberts syndrome and its frequency varied from 8% to 30%. In metaphases with PCD of one and of two chromosomes, the chromosome involved were identified, and chromosome 3 was involved 21 times among 59 chromosomes with PCD. Chromosome 3 tends to be preferentially involved in dicentric formation. In lymphocyte cultures from the same patients there were no metaphases with PCD, but there was a slight increase of breaks and the presence of dicentric chromosomes, also involving chromosome 3. Polyploid metaphases were increased in some of the cases. Karyotypic variation can be considered a cellular phenotypic characteristic of TS in fibroblasts cultured from the skin lesions, and its type indicates disturbances in the mechanics of centromere division and of chromosome distribution at cell division.     

Homozygotes for the autosomal dominant neoplasia syndrome (MEN1).

Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, we had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However, the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development.     

Chlorophyllous and Achlorophyllous Specimens of <Emphasis Type="Italic">Epipactis microphylla</Emphasis> (Neottieae,Orchidaceae) Are Associated with Ectomycorrhizal Septomycetes,including Truffles

Mycoheterotrophic species (i.e., achlorophyllous plants obtaining carbon from their mycorrhizal fungi) arose many times in evolution of the Neottieae, an orchid tribe growing in forests. Moreover, chlorophyllous Neottieae species show naturally occurring achlorophyllous individuals. We investigated the fungal associates of such a member of the Neottieae, Epipactis microphylla, to understand whether their mycorrhizal fungi predispose the Neottieae to mycoheterotrophy. Root symbionts were identified by sequencing the fungal ITS of 18 individuals from three orchid populations, including achlorophyllous and young, subterranean individuals. No rhizoctonias (the usual orchid symbionts) were recovered, but 78% of investigated root pieces were colonized by Tuber spp. Other Pezizales and some Basidiomycetes were also found. Using electron microscopy, we demonstrated for the first time that ascomycetes, especially truffles, form typical orchid mycorrhizae. All identified fungi (but one) belonged to taxa forming ectomycorrhizae on tree roots, and four of them were even shown to colonize surrounding trees. This is reminiscent of mycoheterotrophic orchid species that also associate with ectomycorrhizal fungi, although with higher specificity. Subterranean and achlorophyllous E. microphylla individuals thus likely rely on tree photosynthates, and a partial mycoheterotrophy in individuals plants can be predicted. We hypothesize that replacement of rhizoctonias by ectomycorrhizal symbionts in Neottieae entails a predisposition to achlorophylly.     

The pressure/volume relationship during dobutamine stress echocardiography in transplanted heart: comparison with quality of life and coronary anatomy

Background

Cardiac allograft vasculopathy (CAV) is a major late complication in cardiac transplant recipients and has a relevant impact on outcome of these patients. Aims of this study: to compare, in cardiac transplant recipients patients, the diagnostic value of pressure/volume relationship (ESPVR) during dobutamine stress echocardiography (DSE) for coronary artery disease, assessed by Multislice Computed Tomography (MSCT), and by coronary angiography (CA). We also analyzed any possible relationship between ESPVR and the Health Related Quality of Life of the patients (HRQoL), evaluated by SF–36 questionnaire.

Methods

25 consecutive patients underwent DSE within 24 hours after MSCT coronary angiogram and then they underwent CA. The HRQoL questionnaire was administered to the patients in the settings of DSE. They were followed-up for 6 months.

Results

DSE has a sensitivity in detecting CAV of 67%, specificity of 95%, positive predictive value of 67% and negative predictive value of 95%; DSE with ESPVR has a sensitivity of 100%, specificity of 95%, positive predictive value of 75%, negative predictive value of 100%; MSCT has a sensitivity of 100%; specificity of 82%; positive predictive value of 43%; negative predictive value of 100%. Htx recipients with a flat-biphasic ESPVR, although asymptomatic, perceived a worst HRQoL compared with the up-sloping ESPVR population, and this is statistically significant for the general health (p 0.0004), the vitality (p 0.0013) and the mental health (p 0.021) SF-36 subscale.

Conclusions

Evaluation with DSE and ESPVR is accurate in the clinical control of heart transplant recipients reserving invasive evaluation only for patients with abnormal contractility indexes.     

Chromosome instability in lymphocytes from a patient with Werner's syndrome is not associated with DNA repair defects

Different cellular parameters used to detect genetic instability were analyzed in lymphocytes from a patient affected by Werner's syndrome (WS). Cytogenetic studies indicated the presence of structural and numerical chromosomal abnormalities and the occurrence of variegated translocation mosaicism. The baseline mutation frequency was similar to that observed in normal donor samples. DNA repair investigations showing a normal capability to perform UV-induced DNA repair synthesis and a normal sensitivity to various mutagens (UVC light, mono- and bi-functional alkylating agents) indicate that different DNA repair mechanisms act normally in WS. In this feature, WS appears to differ from the other genetically determined syndromes in which chromosomal instability is associated with a marked hypersensitivity to specific DNA-damaging agents.     

Women heterozygous for deficiency of the (p21 leads to pter) region of the X chromosome are fertile

A woman balanced carrier of a X/15 translocation gave birth to a balanced infertile son and three unbalanced Xp--fertile daughters. This family and the other eleven cases of Xp--fertile women found in the literature demonstrate that loss of the p21 leads to pter region of the X chromosome is compatible with fertility, probably because it leaves on Xp the region which is never inactivated.     

Clonal structural chromosomal rearrangements in primary fibroblast cultures and in lymphocytes of patients with Werner's syndrome

Summary The cytogenetics of six cases of adult progeria (Werner's syndrome) from three Sardinian families were investigated. The overall increased incidence of chromosome breakage found in cultured lymphocytes and fibroblasts seems to be age-dependent. The occurrence of clonal variegated translocation mosaicism, previously found by other authors in fibroblast cell lines derived from Werner patients was demonstrated also in fibroblasts analyzed in situ on the outgrowth halos from primary skin explants; a strong indication that these aberrations are present in the in vivo precursors. The same type of clonal structural aberration was found for the first time also in 72h-cultured lymphocytes. These findings demonstrate that Werner's syndrome is indeed a further example of a chromosome rearrangement syndrome.     

Women heterozygous for deficiency of the (p21 → pter) region of the X chromosome are fertile

Summary A woman balanced carrier of a X/15 translocation gave birth to a balanced infertile son and three unbalanced Xp- fertile daughters. This family and the other eleven cases of Xp- fertile women found in the literature demonstrate that loss of the p21 pter region of the X chromosome is compatible with fertility, probably because it leaves on Xp the region which is never inactivated.