Witteveen-Kolk syndrome (WITKOS) is a rare, autosomal dominant neurodevelopmental disorder caused by heterozygous loss-of-function alterations in the SIN3A gene. WITKOS has variable expressivity that ...commonly overlaps with other neurodevelopmental disorders. In this study, we characterized a distinct DNA methylation epigenetic signature (episignature) distinguishing WITKOS from unaffected individuals as well as individuals with other neurodevelopmental disorders with episignatures and described 9 previously unpublished individuals with SIN3A haploinsufficiency.
We studied the phenotypic characteristics and the genome-wide DNA methylation in the peripheral blood samples of 20 individuals with heterozygous alterations in SIN3A. A total of 14 samples were used for the identification of the episignature and building of a predictive diagnostic biomarker, whereas the diagnostic model was used to investigate the methylation pattern of the remaining 6 samples.
A predominantly hypomethylated DNA methylation profile specific to WITKOS was identified, and the classifier model was able to diagnose a previously unresolved test case. The episignature was sensitive enough to detect individuals with varying degrees of phenotypic severity carrying SIN3A haploinsufficient variants.
We identified a novel, robust episignature in WITKOS due to SIN3A haploinsufficiency. This episignature has the potential to aid identification and diagnosis of individuals with WITKOS.
Unmanned Aerial Vehicles (UAVs), or drones, offer the ability to collect cost-effective fine-scale imagery that is suitable for the capture of concurrent hydrodynamic and faunal data within tidal ...stream environments. This is a necessary stage of information gathering to inform tidal energy device design, advise control and maintenance strategies and better inform environmental consenting processes. For this study a total of sixty-three UAV surveys were undertaken within the Inner Sound of the Pentland Firth, Scotland, UK, over two 4-day periods in 2016 and 2018. The aims of this data collection effort were to characterise bathymetrically driven hydrodynamic features, comprising of kolk-boil distribution, presence, and area, as well as marine life such as seabird distributions, presence, and orientation relative to the flow. To achieve this, a method to extract quantifiable metrics from UAV imagery was required. This paper details the processes and methodology to create a graphical user interface (GUI) to provide these outputs rather than examining specific results. It includes an explanation of the criteria that the GUI needed to meet to be able to process the imagery, a description of the workflow and an explanation of the sub-routines required such as image registration and calibration. The outputs of the GUI, and their relevance to tidal energy developments, are also discussed. Finally, this paper details future work incorporating computer vision techniques to improve the accuracy, reliability, and processing speed of the GUI.
Pubertal delay can be due to hypogonadotropic hypogonadism (HH), which may occur in association with anosmia or hyposmia and is known as Kallmann syndrome (OMIM #308700). Recently, hypogonadotropic ...hypogonadism has been suggested to overlap with Witteveen-Kolk syndrome (WITKOS, OMIM #613406) associated with 15q24 microdeletions encompassing
. Whether hypogonadotropic hypogonadism is due to haploinsufficiency of
or any of the other eight genes present in 15q24 is not known. We report the case of a female patient with delayed puberty associated with intellectual disability, behavior problems, dysmorphic facial features, and short stature, at the age of 14 years. Clinical, laboratory, and imaging assessments confirmed the diagnosis of Kallmann syndrome. Whole-exome sequencing identified a novel heterozygous frameshift variant, NM_001145358.2:c.3045_3046dup, NP_001138830.1:p.(Ile1016Argfs*6) in
, classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG/AMP) criteria. Reverse phenotyping led to the clinical diagnosis of WITKOS. No other variant was found in the 96 genes potentially related to hypogonadotropic hypogonadism. The analysis of the other contiguous seven genes to
in 15q24 did not reveal any clinically relevant variant. In conclusion, these findings point to
as the gene in 15q24 related to the reproductive phenotype in patients with overlapping WITKOS and Kallmann syndrome.
S staranjem prebivalstva narašča tudi število totalnih artroplastik velikih sklepov pri bolnikih z degenerativnimi boleznimi sklepov. Po drugi strani so finančna sredstva zdravstvenega proračuna ...omejena ali se celo zmanjšujejo. Koncept kirurgije s pospešenim okrevanjem (KSPO), s katerim skrajšamo ležalno dobo bolnikov, ne da bi s tem ogrozili kakovost zdravljenja, koristi tako bolniku, kot tudi bolnišničnemu proračunu.
Koncept KSPO smo v SB Jesenice pri bolnikih za primarno totalno artroplastiko kolka in kolena začeli uvajati v letu 2014. Postopno smo ga optimizirali in nadgradili, med drugim z izobraževanjem bolnikov in njihovih svojcev pred operacijo, ter v letu 2015 vse bolnike za primarno totalno artroplastiko kolena ali kolka v celoti obravnavali v skladu z načeli KSPO.
Analizirali smo izid zdravljenja s primerjavo ležalne dobe. Mediana vrednost je pred uvedbo KSPO v letih 2013 in 2014 znašala 6,45 oz. 6,4 dni. Po uvedbi KSPO se je le-ta pomembno skrajšala. Mediana vrednost je v letih 2015, 2016 znašala 4,4 dni, v letu 2017 pa 3,5. Analizirali smo tudi pogostost ponovnih sprejemov v 30 dneh po odpustu iz bolnišnice, kjer med bolniki pred in po uvedbi KSPO ne ugotavljamo pomembnih razlik.
Koncept KSPO smo na ortopedskem oddelku SB Jesenice uspešno uvedli in tako učinkovito skrajšali ležalno dobo bolnikov po totalni artroplastiki kolena ali kolka, ne da bi ob tem povečali stopnjo zapletov. To smo dosegli z večdisciplinarnim pristopom k obravnavi bolnikov pred (izobraževanje) in med hospitalizacijo, z optimizacijo nadzora izgube krvi (rutinska uporaba traneksamične kisline) in preprečevanja bolečine (multimodalni pristop k analgeziji brez opioidov) ter z optimizacijo fizioterapije.
Characteristics of turbulent flow around a braided bar are much more complex as compared to the straight and meandering rivers. The impact of a mid-channel bar on the turbulent flow structure has ...been investigated in this research. A new dominance function S
i
,
H
is proposed in this study as a measure of the relative dominance of ejection and sweep events in turbulent flow structure. Occurrence of the kolk-boil phenomenon is observed due to interaction of ejection and sweep events. The kolk-boil phenomenon generates negative pressure gradients which result in suspension of bed sediment particles in the flow domain. The transition probability of bursting event movements is computed using the first Markov chain. A new parameter movement ratio is formulated in this study, which is found to faithfully reflect the fluvial processes of sedimentation and scouring on the channel bed. Acceleration of flow is seen to occur at adjoining regions close to the upstream end of the bar. Due to the presence of the bar, the flow area in its proximity decreases which has caused increment in the velocity at sections located near the upstream end of the mid-channel bar. For model runs with bars, a distinct bulge in the turbulent intensity graph is observed. The mid-channel bar effect is mainly discernible in the lower layers of flow.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: The Witteveen-Kolk syndrome (WITKOS) (OMIM: 613406) is a heterogeneous emerging disorder caused by pathogenic variants or microdeletions encompassing the SIN3A gene (SIN3 Transcription ...Regulator Family Member A). It is characterized by distinctive facial features, developmental delay, intellectual disability, microcephaly, short stature, and subtle anomalies on brain magnetic resonance imaging (MRI). To date, about 50 patients have been reported in the medical literature. Patient Presentation: In this article, we reported a patient with classic findings of WITKOS including global developmental delay, microcephaly, hypotonia, vomiting, malnutrition, autistic and dysmorphic facial features, and cardiac abnormalities. Also, a barium esophagogram suggested severe motility disorder and gastroesophageal reflux disease. Affymetrix CytoScan 750K microarray showed a de novo 1.6-Mb deletion at 15q24.1q24.2, including the whole SIN3A gene. We have also summarized the clinical features of WITKOS patients in the medical literature and cardiac abnormalities detected in 4 out of 10 patients in studies that clearly state that cardiac examination was performed in the patients. Conclusion: Our findings showed that cardiac defects are not uncommon findings in WITKOS. Physicians should also be aware of reflux disease and motility disorder in patients with feeding difficulty together with early cardiac examination in terms of an improved quality of life in WITKOS patients.
Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. More than 40 genes have been associated with the pathogenesis of CHH, but most cases still remain without ...a molecular diagnosis. Mutations involving the same gene (e.g., FGFR1, PROK2/PROKR2, CHD7) were found to cause normosmic CHH and Kallmann syndrome (KS), with and without associated phenotypes, illustrating the coexistence of CHH with signs of other complex syndromes. The Witteveen-Kolk syndrome (WITKOS), caused by defects of the SIN3A gene, is a heterogeneous disorder characterized by distinctive facial features, microcephaly, short stature, delayed cognitive, and motor development. Although micropenis and cryptorchidism have been reported in this syndrome, WITKOS has not been formally associated with CHH so far.
A man with KS associated with mild syndromic features (S1) and a boy with global developmental delay, syndromic short stature, micropenis and cryptorchidism (S2), in whom common genetic defects associated with CHH and short stature had been previously excluded, were studied by either chromosomal microarray analysis or whole exome sequencing.
Rare SIN3A pathogenic variants were identified in these 2 unrelated patients with CHH phenotypic features. A 550 kb deletion at 15q24.1, including the whole SIN3A gene, was identified in S1, and a SIN3A nonsense rare variant (p.Arg471*) was detected in S2.
These findings lead us to propose a link between SIN3A defects and CHH, especially in syndromic cases, based on these 2 patients with overlapping phenotypes of WITKOS and CHH.
Witteveen–Kolk syndrome: The first patient from Turkey Ercoskun, Pelin; Yuce Kahraman, Cigdem
American journal of medical genetics. Part A,
February 2021, 2021-02-00, 20210201, Letnik:
185, Številka:
2
Journal Article
Recenzirano
Witteveen–Kolk syndrome is a rare genetic disorder characterized by intellectual disability, developmental delay and dysmorphic facial features including a long face with prominent forehead, ...depressed nasal bridge, long‐smooth philtrum and malformed ears. Skeletal abnormalities, microcephaly and malformation of the brain are other findings. This syndrome is caused by mutations in the SIN3A gene or microdeletions encompassing this gene. The protein encoded by SIN3A gene plays a regulatory role in the control of various developmental processes, especially cortical expansion and maturation. To date, 17 patients have been reported in the medical literature. In this article, we reported a patient with Witteveen–Kolk syndrome who had a retrognathia as an unusually finding. To the best of our knowledge, this is the first patient of Witteveen–Kolk syndrome reported from Turkey.
PDF
