46 research outputs found
The power of the Mediator complex-Expanding the genetic architecture and phenotypic spectrum of MED12 -related disorders
MED12 is a member of the large Mediator complex that controls cell growth, development, and differentiation. Mutations in MED12 disrupt neuronal gene expression and lead to at least three distinct X-linked intellectual disability (XLID) syndromes (FG, Lujan-Fryns, and Ohdo). Here we describe six families with missense variants in MED12 (p.(Arg815Gln), p.(Val954Gly), p.(Glu1091Lys),p.(Arg1295Cys), p.(Pro1371Ser) and p.(Arg1148His), the latter being firstly reported in affected females) associated with a continuum of symptoms rather than distinct syndromes. The variants expanded the genetic architecture and phenotypic
spectrum of MED12-related disorders. New clinical symptoms included brachycephaly, anteverted nares, bulbous nasal tip, prognathism, deep set eyes, and single palmar crease. We
showed that MED12 variants, initially implicated in X-linked recessive disorders in males, may predict a potential risk for phenotypic expression in females, with no correlation of the X chromosome inactivation pattern in blood cells. Molecular modeling (Yasara Structure) performed to model the functional effects of the variants strongly supported the pathogenic character of the variants examined. We demonstrated that molecular modeling is a useful method for in silico testing of potential functional effects of MED12 variants and thus can be a valuable addition to the interpretation of the clinical and genetic findings
Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care
Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221
Variants in CUL4B are Associated with Cerebral Malformations
Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B
Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care
Purpose: Mowat–Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype–phenotype correlations of MWS. Methods: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluati
Nutrition and dental caries. Part IV. Results of a histological study on dentition in albino rats fed cariogenic diets supplemented with vitamins A and D
Nutrition and dental caries. II. Histological picture of teeth in the rat with experiment dental caries
Camouflage as the additional form of protection during special operations
Despite the increasing dominance of electronic detection devices, one of the most efficient ways to ensure safety and protection of people and equipment are activities associated with camouflage aimed at hiding these "objects" from the sight and the equipment of the opponent. The paper presents a definition of camouflage and its types. It also discusses the requirements for various groups of camouflaging products gathered on the basis of the applicable standards in force and other regulations in this regard. The paper contains examples of state-of-the-art solutions for multidimensional products, which ensure camouflage against detection devices within the range of visibility, near infrared, thermal and radiolocation. It also presents the newest achievements in the field of camouflage patterns, as well as methods of attaining camouflage camouflage effects applied by global manufacturers of military products
Ocena i weryfikacja funkcjonalności nowych wieloskładnikowych materiałów maskujących
The article presents new textile structures (woven and knitted fabrics) featuring camouflage properties in visible (VIS) and near infra-red (IR) radiation bands. The textiles were designed and made for masking individuals and their personal equipment. Their design, diversified by applied yarns, weaves and way of distribution of metalised yarns on the surface of fabrics is discussed. Levels of the resulting physical, mechanical and functional parameters of woven and knitted fabrics are presented, both raw and after finishing treatment.W artykule przedstawiono badania nad nowymi lekkimi konstrukcjami włókienniczymi przeznaczonymi do maskowania ludzi i ich bezpośredniego wyposażenia ukierunkowane na skuteczność maskowania w świetle widzialnym (VIS) i bliskiej podczerwieni (IR). Omówione zostały rezultaty badań w zakresie doboru składu surowcowego oraz następnych procesów przetwórczych do etapu wykończalniczego w aspekcie spełnienia złożonych poziomów parametrów odzwierciedlających właściwości funkcjonalne
The materials featuring electro-conductivity being applied into highly specialised products
Surowce o właściwościach elektroprzewodzących zyskują obecnie coraz szersze zastosowanie w wyrobach wysokospecjalistycznych przeznaczonych, między innymi do maskowania w tym antyradiolokacyjnego. Zawierają one w swojej konstrukcji różnego typu surowce metalowe lub z elementami metalowymi oraz węglowymi o specjalnych właściwościach. W artykule dokonano przeglądu nowoczesnych surowców elektroprzewodzących wytwarzanych na świecie w tym: włókien i przędz metalowych, przędz z zawartością włókien metalowych, włókien i przędz metalizowanych, przędz z włókien zawierających wewnątrz lub na powierzchni różne dodatki elektroprzewodzące, przędz z włókien węglowych.The materials featuring electro-conductivity currently find more and more wide applications in highly specialised products dedicated ia. for masking purposes, including anti-radar ones. The materials contain within their structure various types of metal or metal and carbon compounds featuring special properties. The article covers a review of modern electro- conductive materials being manufactured worldwide, including: metal fibres and yarns, yarns with metal fibres added, metallised fibres and yarns, yarns of fibres which contain some electro-conductive additions inside or on surface, yarns of carbon fibres