Hidrotic ectodermal dysplasia in a Chinese pedigree:A case report

BACKGROUND We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia(HED)with a variation in GJB6(c.31G>A).The patients in the family had a triad of clinical manifestations of varying degrees.Although the same variation locus have been reported,the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder,palmoplantar keratosis,and congenital hypotrichosis.CASE SUMMARY This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED.The proband(IV4)was a male patient with normal sweat gland function and dental development,no skeletal dysplasia,no cognitive disability,and no hearing impairments.His parents were not consanguineously married.Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longit-udinal ridges,in addition to mild bilateral palmoplantar hyperkeratosis.GJB6,GJB2,and GJA1 have been reported to be the causative genes of HED;therefore,we subjected the patient’s samples to Sanger sequencing of these three genes.In this family,the variation locus was at GJB6(c.31G>A,p.Gly11Arg).Overex-pression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models,and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot,respectively.CONCLUSION We report another HED phenotype associated with GJB6 variations,which can help clinicians to diagnose HED despite its varying presentations.

INDUCTION OF ECTODERMAL CELLS FROM VEGETALENDODERMAL BLASTOMERES OF AMPHIOXUS(BRANCHIOSTOMA BELCHERI TSINGTAUNESE) EMBRYOS BY THE CALCIUM IONOPHORE A23187

Timing of vegetal-endodermal cell determination in amphioxus embryos remains uncertain. We tentatively testal effects of A23187, the calcium ionophore, on the deveopment of vegetal blastomeres isolated at the 16-cell stage. It was found that when vegetal blastomres committed to endodermwere treated with A23187 prior to gastrulation, they were transformed into ectodermal cells as evidenced by the cell morphology and function characteristic of epidermis. Howver, the developmental fate of the sam blastomeres untreated or treated with DMSO at the same stage or of those treated with A23187 after gastrulation remained unchanged. Thus, vegetal-endodermal cells in amphioxus embryos are not irreversibly deermined before the gastrula stage, and artificial incarease in intracelluar Ca2+ concentration can induce transdetermination of the predetermined endodermal cells into ectodermal cells.

Clinical features, surgical outcomes and genetic analysis of ectodermal dysplasia with ocular diseases

AIM: To report on the clinical features, surgical outcomes and gene mutation analysis of three ectodermal dysplasia probands with ocular diseases. METHODS: A case-note review of three unrelated probands diagnosing with ectodermal dysplasia with ocular diseases was undertaken. Patient clinical features and the outcomes of surgery were analysed. The suspected pathogenic genes were analysed by whole exome sequencing from patients with ectodermal dysplasia and Sanger sequencing from family members.RESULTS: The ocular clinical features of ectodermal dysplasia with ocular diseases mainly include eyelid ectropion, lagophthalmos and absence of lacrimal punctum. All the probands underwent surgeries of full-thickness free skin flap grafting to correct ectropion. They achieved good recovery, and there were no obvious complications during the follow-up. The gene sequencing results did not show any meaningful genetic mutations.CONCLUSION: Lid ectropion is one of the key clinical traits of ectodermal dysplasia with ocular diseases. Ectropion correction with full-thickness free skin flap grafting is an effective procedure to correct ectropion for ectodermal dysplasia patients with ichthyosis-like tissue. The suspected pathogenic genes of ectodermal dysplasia with ectropion should be further verified or confirmed by large samples of the family.

Maxillo-mandibular rehabilitations with very early osteointegrated dental implants for severe hypodontia and anodontia related to ectodermal dysplasia

The ectodermal dysplasias are rare diseases with hypodontia, hypotrichosis and hypohidrosis. The subject's life is considerably constrained and this from an early age, with major difficulties for the integration and acceptance of conventional prosthetic occlusal rehabilitation. The use of implants is an integral part of early treatment, in the regions of stable growth, that is to say symphysis. In two childs of 5 and 6 years we have made implant-borne prosthetic rehabilitation in the maxilla and the mandible. Aesthetic and social evaluation were positive. We have restored the normal oro-facial functions for the correct development of skeletal bases. They acted as an external fixator intraoral, stimulating the growth by the function. Our question was: can we leave a child throughout his childhood and adolescence with a not suitable removable prosthesis, under the pretext of growth unfinished?

Prenatal diagnosis of anhidrotic ectodermal dysplasia with unconventional loci abnormalities： a case report

Anhidrotic ectodermal dysplasia （EDA） is a relatively rare congenital hereditary disease. Because of a reduced number of sweat glands, patients are unable to perspire and consequently suffer from hyperthermia and infection. This is a potential cause of death in childhood. Domestic prenatal diagnosis methods focus on genetic diagnosis. But for some conditions, because of the uncertain molecular pathology, we need other methods to assist to in prenatal diagnosis. Here, we report one case of a new mutation locus which may be associated with EDA and the prenatal diagnosis of EDA by fetal skin biopsy under fetoscopy in mid pregnancy, combined with a review of the literature.

Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome:a rare entity

Ectrodactyly-ectodermic dysplasia-cleft lip/palate(EEC)syndrome is a rare congenital anomaly of inherited origin and varying clinical features.This syndrome has three main symptoms,which display variable expression and penetrance.The management of this syndrome is challenging,with few reports in the medical literature.We present a case of a 22-year-old boy with EEC syndrome and offer insight into current knowledge about this syndrome.

Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling

The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic development.Our recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its formation.Here,we demonstrate that through brief inhibition of Nodal signaling in vitro,mouse embryonic stem cell(ESC)-derived epiblast stem cells(ESD-EpiSCs)could be committed to transient ectodermal progenitor populations,which possess the ability to give rise to neural or epidermal ectoderm in the absence or presence of BMP4,respectively.Mechanistic studies reveal that BMP4 recruits distinct transcriptional targets in ESD-EpiSCs and ectoderm-like cells.Furthermore,FGF–Erk signaling may also be alleviated during the generation of ectoderm-like cells.Thus,our data suggest that instructive interactions among several extracellular signals participate in the commitment of ectoderm from ESD-EpiSCs,which shed new light on the understanding of the formation of ectoderm during the gastrulation in early mouse embryo development.

The inverted retina and the evolution of vertebrates:an evo-devo perspective

The inverted retina is a basic characteristic of the vertebrate eye.This implies that vertebrates must have a common ancestor with an inverted retina.Of the two groups of chordates,cephalochordates have an inverted retina and urochordates a direct retina.Surprisingly,recent genetics studies favor urochordates as the closest ancestor to vertebrates.The evolution of increasingly complex organs such as the eye implies not only tissular but also structural modifications at the organ level.How these configurational modifications give rise to a functional eye at any step is still subject to debate and speculation.Here we propose an orderly sequence of phylogenetic events that closely follows the sequence of developmental eye formation in extant vertebrates.The progressive structural complexity has been clearly recorded during vertebrate development at the period of organogenesis.Matching the chain of increasing eye complexity in Mollusca that leads to the bicameral eye of the octopus and the developmental sequence in vertebrates,we delineate the parallel evolution of the two-chambered eye of vertebrates starting with an early ectodermal eye.This sequence allows for some interesting predictions regarding the eyes of not preserved intermediary species.The clue to understanding the inverted retina of vertebrates and the similarity between the sequence followed by Mollusca and chordates is the notion that the eye in both cases is an ectodermal structure,in contrast to an exclusively(de novo)neuroectodermal origin in the eye of vertebrates.This analysis places cephalochordates as the closest branch to vertebrates contrary to urochordates,claimed as a closer branch by some researchers that base their proposals in a genetic analysis.

A mathematical Model for Inter-Cellular Inductive

In vertebrate limb, a group of specialized epithelial cells called Apical Ectodermal Ridge (AER) form at the boundary of dorsal and ventral limb ectoderm. Recent experiments suggest that AER forms at the boundary of Fringe expressing and Fringe non-expressing cells by a specific type of receptor-ligand interaction called as inductive signaling, involving the transmembrane proteins Notch, Serrate and Delta. Experiments conducted on Drosophila wing disc have shown that Fringe inhibits the binding ability of Serrate ligand to Notch and enhances that of Delta to Notch. Although several of the signaling elements have been identified experimentally, it remains unclear how the inter-cellular interactions can give rise to such a boundary of specialized cells. Here we present an ordinary differential equation (ODE) model involving Delta→Notch and Serrate→Notch interactions between juxtaposed Fringe expressing and Fringe nonexpressing cells. When simulated in a compartmentalized set up, this model gives rise to high Notch levels at the boundary of Fringe expressing and Fringe non-expressing cells.

Midline Spinal Cord Hamartomas—A Report of Six Cases

Midline Spinal Cord Hamartomas are relatively rare and asymptomatic. These lesions may present with a tethered cord and a normal overlying skin, a skin dimple, a dermal sinus tract or dense collagen. Most patients have few or no neurological symptoms related to them. Microscopically they are composed of mature and well-differentiated ectodermal and mesodermal elements, meningothelial cells, calcification, and even urothelium. We report MRI and histologic features of midline spinal cord hamartomas in six cases.

Role of Smad4 from ocular surface ectoderm in retinal vasculature development

●AIM:To investigate how signals from lens regulate retinal vascular development and neovascularization.●METHODS:Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively.Standard histological and whole-mount retina staining were employed to reveal morphological changes of retinal vasculature in Smad4 defective eye.cDNA microarray and subsequent analyses were conducted to investigate the molecular mechanism underlying the vascular phenotype.Quantitative polymerase chain reaction(qPCR)was carried out to verify the microarrays results.●RESULTS:We found that inactivation of Smad4 specifically on surface ectoderm leads to a variety of retinal vasculature anomalies.Microarray analyses and qPCR revealed that Sema3 c,Sema3 e,Nrp1,Tie1,Sox7,Sox17,and Sox18 are significantly affected in the knockout retinas at different developmental stages,suggesting that ocular surface ectoderm-derived Smad4 can signal to the retina and regulates various angiogenic signaling in the retina.●CONCLUSION:Our data suggest that the cross-talk between ocular surface ectoderm and retina is important for retinal vasculature development,and Smad4 regulates various signaling associated with sprouting angiogenesis,vascular remodeling and maturation in the retina of mice.

Tonsil-derived stem cells as a new source of adult stem cells

Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.

Acro-dermato-ungual-lacrimal-tooth syndrome:case report

Acro-dermato-ungual-lacrimal-tooth syndrome （ADULT syndrome, OMIM 103285） is a rarely seen ectodermal dysplasia disorder first described by Propping and Zerres in 1993. ADULT syndrome is known as an autosomal dominant disorder. Only a family constellation and four independent cases were reported worldwide up to now. Here, we report a case of ADULT syndrome, which is the first case reported from China.

Assessment of Bisphenol A(BPA) neurotoxicity in vitro with mouse embryonic stem cells

The adverse effects of environmental pollution on our well-being have been intensively studied with many in vitro and in vivo systems. In our group, we focus on stem cell toxicology due to the multitude of embryonic stem cell（ESC） properties which can be exerted in toxicity assays. In fact, ESCs can differentiate in culture to mimic embryonic development in vivo, or specifically to virtually any kind of somatic cells. Here, we used the toxicant Bisphenol A（BPA）, a chemical known as a hazard to infants and children, and showed that our stem cell toxicology system was able to efficiently recapitulate most of the toxic effects of BPA previously detected by in vitro system or animal tests. More precisely, we demonstrated that BPA affected the proper specification of germ layers during our in vitro mimicking of the embryonic development, as well as the establishment of neural ectoderm and neural progenitor cells.

Studying developmental neurotoxic effects of bisphenol A(BPA) using embryonic stem cells

There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is limited information available on their effects on neural development（Betts,2010;US EPA,2015）.

Docking and 3D-QSAR Studies on the Imidazo[1,5-c]pyrimidine Derivative as EED Inhibitors

Embryonic ectoderm development(EED)has become a novel target for cancer treatment.In this study,a series of EED inhibitors was subjected to a three-dimensional quantitative structure-activity relationship(3D-QSAR)and molecular docking.Accordingly,this is the first of such 3D-QSAR studies in a series of EED inhibitors displaying anti-cancer pharmacological profiles.The CoMFA(q^(2)=0.792,r^(2)=0.994,r^(2)pred=0.74)and CoMSIA(q^(2)=0.873,r2=0.994,r^(2)pred=0.81)models demonstrated good robustness and predictive ability.Moreover,molecular docking suggested that cation-π,π-π stacking and hydrogen bonding interactions were the main factors affecting the activity of these inhibitors.Five new small molecules were designed based on the CoMFA and CoMSIA contour maps.These molecules were then submitted to further ADME studies,in which the ADME properties of the five designed molecules were found to be within a reasonable range.In view of the corresponding findings,this study may provide theoretical guidance for the rational design of novel EED inhibitors.