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

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

Analiza porównawcza badań odporności na uderzenie wielowarstwowych tekstylnych ochron przeciwuderzeniowych kończyn dolnych

The article features the requirements and testing methodology for the assessment of the impact strength of multilayer lower limb protectors designed for the police, described in “HOSDB Blunt Trauma Protector Standard for UK Police. Limb and Torso Protectors” and BS 7971:2002 “Protective clothing and equipment for use in violent situations and in training”. The paper also presents an analysis of laboratory test results of lower limb protectors, which were conducted in conformity with the requirements of both standard documents. An attempt was also made to compare them in terms of future application.W artykule scharakteryzowano wymagania i metodykę badawczą dotyczącą oceny odporności na uderzenie wielowarstwowych włókienniczych ochraniaczy przeznaczonych dla policji, zawartych w dokumentach: „HOSDB Blunt Trauma Protector Standard for UK Police. Limb and Torso Protectors” i BS 7971:2002 „Protective clothing and equipment for use in violent situations and in training”. Przedstawiono analizę wyników badań laboratoryjnych ochraniaczy kończyn dolnych wykonanych zgodnie z wymaganiami obydwu dokumentów normatywnych. Podjęto próbę ich porównania z uwzględnieniem aspektu zastosowania w przyszłości

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

Relationship between molecular, cytogenetic and clinical parameters in 63 individuals with full mutation in FMR1 gene

Relationship between selected molecular, cytogenetic and clinical parameters was analysed in a group of 63 individuals (45 males and 18 females) with full fragile X mutation. Significant correlation between the size and somatic instability of fully mutated alleles in both males and females was found. Possible explanations of this result are discussed. With respect to the mutation size, an apparent difference was observed between males with different degree of mental retardation. No such difference appeared when affected and normal females with full mutation were compared. The proportion of mutated active X chromosome was significantly higher in mentally retarded females than in those without any mental impairment

Indentification of three different chromosomal additions by chromosome painting using fluorescence in situ hybridization [FISH] technique

Fluorescence in situ hybridization (FISH) is a very useful method for assessing chromosome rearrangements. When neither banding pattern nor clinical symptoms are sufficient to determine the origin of additional chromosomal fragment, FISH with multiple chromosome-specific libraries (chromosome painting), allows to solve this diagnostic problem rapidly. Three chromosomal additions, 7q+, 13p+ and 22q+, found in routine cytogenetic studies performed in children with phenotypic abnormalities were analysed using FISH. This technique documented the origin of the extra material to be derived from chromosome 16[der(7)t(7; 16)(q36.3;p 13.11)], 18[der(13)t(13; 18)(p12;q 12.2)] and 22[dup(22)(q11.2q13.1)], respectively. In two cases the abnormality arose de novo, while in the third case the product of translocation t(13;18) was maternal by origin. It was present in 30% of mother's lymphocytes, and in 70% of them a balanced Robertsonian translocation t(13q;15q) was found. In the presented cases the chromosome analysis with both traditional banding and chromosome painting techniques, allowed to establish final clinical diagnosis

Supernumerary marker chromosomes characterized by fluorescence in situ hybridization [FISH]

Until recently marker chromosomes have presented a difficult diagnostic problem for cytogeneticists as well as for clinicians. Introduction of FISH to cytogenetic analysis has enabled identification of their origin giving possibility to outline specific phenotypic effects of defined marker chromosomes. Nine marker chromosomes were analysed with FISH using centromeric probes, chromosome- specific libraries and unique DNA sequences probes for PWS/AS critical region. The origin from acrocentric chromosomes was established in 6 cases. One marker was a product of maternal 11;22 translocation and two others were pericentromeric regions of chromosome 2 and 4. Among 6 markers, derived from acrocentric chromosomes, 2 consisted of pericentromeric part of chromosome 15, one was identified as mar (21) and in 3 other cases the origin could not be differentiated between chromosomes 13 and 21 or 14 and 22. Clinical consequences of marker chromosomes including the risk for chromosomal nondisjunction and trisomy 21 as well as the risk for uniparental disomy (UPD) are discussed

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

Molecular versus classical cytogenetics - evaluation of 20 Prader-Willi syndrome patients

Prader-Willi syndrome (PWS) is a developmental disorder caused by a deficiency of paternal contribution of the chromosome region 15q11.2-q13 arising from differently sized deletions, maternal disomy, or rarely imprinting mutations. We have analyzed 20 PWS patients using combined cytogenetic high resolution technique (HRT), fluorescence in situ hybridization (FISH) and molecular studies to identify parental origin (uniparental disomy) or molecular defect (deletion) of the Prader-Willi region. Lack of a paternal copy of 15q11.2-q13 resulting from its deletion was found in 16 patients. Using high resolution GTG banding on prometaphase chromosomes, deletion in the 15q11.2-q13 region was detected in only 8 patients. Application of FISH with different sets of PWS specific unique sequence probes (D15S11, SNRPN, D15S10, GABRß3) revealed microdeletions in 12 patients. In 12 out of 20 cases FISH confirmed HRT studies, while in 8 cases inconsistent results were obtained. No discrepancies between results of FISH and molecular studies were found, although the latter had a higher sensitivity. We conclude that FISH appears to be a rapid and reliable method of microdeletion identification and should be performed as a method of choice in cytogenetic diagnosis of Prader-Willi syndrome