Microdeletion 1p35.2: a recognizable facial phenotype with developmental delay.

We describe two patients with microdeletion 1p35.2, intrauterine growth retardation, small stature, hypermetropia, hearing impairment and developmental delay. Both patients have long, myopathic facies, with fine eyebrows, small mouths and micrognathia. We postulate a role for the histone deacetylase HDAC1 in the facial phenotype and suggest that deletion of KPNA6 may prevent transmission of the 1p35.2 deletion from affected girls to any offspring through impaired zygotic genome activation.

A case of mosaic trisomy 19q12-q13.2 with high BMI, macrocephaly, and speech delay: does USF2 determine size in the 19q phenotypes?

Hall et al. (2010) describe a boy with mosaic trisomy of the proximal part of 19q, with obesity, macrocephaly and global developmental delay. The patient is interesting with regard to his cytogenetic abnormality, which is smaller than those previously reported, and does not include the candidate obesity and insulin-resistance genes identified by other authors (Zung et al., 2007; Davidsson et al., 2010) as possible causes of the overweight/obesity seen in four of five previously documented patients. This suggests that a novel obesity locus may reside in the duplicated region 19q13.11­q13.2. We present a phenotypically similar boy with intrachromosomal insertion of material derived from proximal 19q into proximal 19p, causing mosaic trisomy 19q12­q13.2, and consider the role of USF2, a master transcriptional regulator of metabolic genes, in 19q phenotypes.

Neurogenic properties and a clinical relevance of multipotent stem cells derived from cord blood samples stored in the biobanks.

Several innovative therapies with human umbilical cord blood stem cells (SCs) are currently developing to treat central nervous system (CNS) diseases. It has been shown that cord blood contains multipotent lineage-negative (LinNEG) SCs capable of neuronal differentiation. Clinically useful cord blood samples are stored in different biobanks worldwide, but the content and neurogenic properties of LinNEG cells are unknown. Here we have compared 5 major methods of blood processing: Sepax, Hetastarch, plasma depletion, Prepacyte-SC, and density gradient. We showed that Sepax-processed blood units contained 10-fold higher number of LinNEG cells after cryopreservation in comparison to all other methods. We showed in this study that multipotent SCs derived from fresh and frozen cord blood samples could be efficiently induced in defined serum-free medium toward neuronal progenitors (NF200+, Ki67+). During neuronal differentiation, the multipotent SCs underwent precise sequential changes at the molecular and cellular levels: Oct4 and Sox2 downregulation and Ngn1, NeuN, and PSD95 upregulation, similar to neurogenesis process in vivo. We expect that data presented here will be valuable for clinicians, researchers, biobanks, and patients and will contribute for better efficacy of future clinical trials in regeneration of CNS.

Immortalisation of human ovarian surface epithelium with telomerase and temperature-sensitive SV40 large T antigen.

Epithelial ovarian cancer is the most common form of gynaecological malignancy. This lethal disease is thought to arise in ovarian surface epithelial (OSE) cells. The biology of these cells is not well understood, due to the limited amount of tissue that can be obtained from a single biopsy and their limited life span in culture. To overcome these problems, we have conditionally immortalised OSE cells with the catalytic subunit of telomerase (hTERT) and a temperature-sensitive form of SV40 Large T antigen (tsT). We have maintained these cells (designated OSE-C2) in culture for more than 100 population doublings after introduction of the immortalising genes. Early passage OSE-C2 cells have a near-tetraploid karyotype and exhibit a dual mesenchymal-epithelial phenotype, with consistent expression of vimentin and variable expression of cytokeratins and type III collagen, and absence of E cadherin expression. OSE-C2 cells proliferate steadily at the permissive temperature of 33 degrees C, but fail to increase in number at the nonpermissive temperature of 39 degrees C. Serum-deprived OSE-C2 cells are stimulated to grow at 33 degrees C by EGF, whereas they are growth inhibited at 33 degrees C by TGFbeta in the presence or the absence of serum. When temperature shifted to the nonpermissive temperature, OSE-C2 cells modulate to a more mesenchymal phenotype, and a proportion of the cells undergo senescence and/or apoptosis. Moreover, at the nonpermissive temperature, the levels of p53 and SV40 Large T antigen diminish, whilst the level of p21 increases, whereas the level of p16 and telomerase activity is unchanged. This experimental system shows that expression of telomerase alone only allows limited proliferative potential of OSE cells; expression of tsT is necessary to maintain these cells in culture for longer periods, perhaps by its ability to inactivate components of the p53/Rb pathway. OSE-C2 cells may be useful in studying the physiology and differentiation of human OSE cells and provide insight into the poorly understood earliest stages of epithelial ovarian cancer.