A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation.

Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype

Schöpf-Schulz-Passarge syndrome: further delineation of the phenotype and genetic considerations.

Schöpf-Schulz-Passarge syndrome is a rare ectodermal dysplasia, characterized chiefly by multiple eyelid apocrine hidrocystomas, palmo-plantar keratoderma, hypodontia, hypotrichosis and nail dystrophy. The clinical spectrum and the most likely inheritance pattern(s) have not yet been completely defined. We report here on two, unrelated patients presenting with additional, previously unreported features, including hypoplastic nipples and optic atrophy. Both individuals were born to consanguineous parents, and one also has affected siblings. A literature review identified 23 additional cases. Multiple eyelid apocrine hidrocystomas, described in all of the cases, are the hallmark of this condition, although they usually appear in adulthood. The concomitant presence of eccrine syringofibroadenoma in most patients and of other adnexal skin tumours in 44% of affected subjects indicates that Schöpf-Schulz-Passarge is a genodermatosis with skin appendage neoplasms. However, the risk of skin and visceral malignancies is not increased. Pedigree study demonstrates that 9 of the 13 published familial cases may be explained by an autosomal recessive mutation, while the remaining pedigrees show apparent vertical transmission compatible with genetic heterogeneity. The benign disease course and advanced age at diagnosis could also suggest locus homogeneity for a recessive mutation with instances of pseudodominant inheritance

Shear strengthening of masonry panels using a gfrp-reinforced mortar coating

The use of new composite materials for reinforcement of heritage masonry structures, especially in seismic prone areas, is of interest structural engineers and conservators. However, the need to increase the structural performance of masonry structures is often in contrast with the principles of conservation in terms of reversibility, limited visual impact, compatibility of new materials with masonry. With the aim at striking a balance between structural safety and heritage protection, this paper investigates strengthening stone and brickwork masonry walls using glass-fiber reinforced polymer (GFRP) meshes embedded into a coating of lime or cement mortar. An experimental research program was undertaken in the laboratory on large-scale wall panels. Both clay brick and stone work specimens were tested, with and without strengthening. Single-sided and double-sided strengthenings were considered, as it is often not practicable to apply the reinforcement to both sides of a wall. Static tests were carried out on twelve masonry panels, under in-plane diagonal shear loading. The mechanisms by which load was carried were observed, varying from the initial, uncracked state, to the final, fully cracked state. The results demonstrate that a significant increase of the in-plane shear capacity of masonry can be achieved by using the proposed retrofitting technique. The experimental data were used to assess the effectiveness of the strengthening, and a finite element (FE) numerical model is discussed and calibrated against experimental results. The FE model was used to investigate further aspects of the reinforced masonry under shear-loading

Mechanical characterization and thermal conductivity measurements using of a new 'small hot-box' apparatus: innovative insulating reinforced coatings analysis

The insulation of the building envelope contributes to the reduction of annual energy consumptions. The development of new materials, such as fibre reinforced insulating coatings, could be useful in order to obtain an effective solution for the improvement of energy performance and for reinforcement of the walls. The evaluation of the thermal and mechanical characteristics of building coatings with good thermal insulation properties and mechanical resistance is the aim of the present paper. A new experimental apparatus, Small Hot-Box, built at the University of Perugia, was used for the evaluation of the thermal conductivity of four different coatings (with and without a reinforced structure). No European standards are available for this innovative facility, but it takes into account some prescriptions of EN ISO 8990. The apparatus was calibrated with materials of known thermal conductivity. The thermal conductivity can be calculated with both the thermal flux meter and the Hot Box method. Good values of the thermal conductivity, in the range of 0.09–0.11 W/mK were found for all the samples, except for one (0.21–0.24 W/mK). Mechanical tests were also carried out in laboratory on all the samples and results were used to evaluate the shear modulus and strength of the wall panels

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan

INTRODUCTION: Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases. METHOD: This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status. RESULTS: Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes. CONCLUSION: Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases

Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between Wiedemann–Steiner and Rubinstein–Taybi syndromes

Lysine-specific methyltransferase 2A (KMT2A) is responsible for methylation of histone H3 (K4H3me) and contributes to chromatin remodeling, acting as \u201cwriter\u201d of the epigenetic machinery. Mutations in KMT2A were first reported in Wiedemann\u2013Steiner syndrome (WDSTS). More recently, KMT2A variants have been described in probands with a specific clinical diagnosis comprised in the so-called chromatinopathies. Such conditions, including WDSTS, are a group of overlapping disorders caused by mutations in genes coding for the epigenetic machinery. Among them, Rubinstein\u2013Taybi syndrome (RSTS) is mainly caused by heterozygous pathogenic variants in CREBBP or EP300. In this work, we used next generation sequencing (either by custom-made panel or by whole exome) to identify alternative causative genes in individuals with a RSTS-like phenotype negative to CREBBP and EP300 mutational screening. In six patients we identified different novel unreported variants in KMT2A gene. The identified variants are de novo in at least four out of six tested individuals and all of them display some typical RSTS phenotypic features but also WDSTS specific signs. This study reinforces the concept that germline variants affecting the epigenetic machinery lead to a shared molecular effect (alteration of the chromatin state) determining superimposable clinical conditions