77 research outputs found
Neurologic phenotypes associated with COL4A1/2 mutations
Objective: To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype–phenotype correlation.
Methods: We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations.
Results: Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype–phenotype correlation did not emerge.
Conclusion: COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall
Australian east coast mid-latitude cyclones in the 20th Century Reanalysis ensemble
Extratropical and subtropical cyclones, and their associated fronts, produce the majority of rainfall and extreme weather in the mid-latitudes around the world. In the Southern Hemisphere in particular, where observations are sparse, we have limited knowledge of their long-term variability and trends. While the long time period of the 20th Century Reanalysis (20CR) offers potential to assess longer-term changes, the lack of observational data sets makes it difficult to assess its reliability. We assess the skill of the 20CR at representing mid-latitude cyclones through a case study on the east coast of Australia. In this region, a comprehensive database has recently been developed of all severe floods between 1871 and 2012, of which >70% are associated with a coastal low-pressure system. Through use of the full 20CR 56-member ensemble, we are able to identify the majority of severe Australian east coast lows as early as the late 19th century, as well as recreate the cyclone tracks for some of the most severe events. The analysis shows that the full ensemble can be used for a long-term assessment of interannual variability in cyclone frequency from at least 1911, despite large inhomogeneities in the ensemble mean pressure fields
The influence of topography on midlatitude cyclones on Australia's east coast
The east coast of Australia has a relatively high frequency of midlatitude cyclones, locally known as East Coast Lows (ECLs), which can cause severe weather including widespread flooding and coastal erosion. The elevated topography close to the east coast has been hypothesized to play a role in both the genesis and impacts of cyclones in this region, but existing studies have been limited to case studies of individual events. In this paper we present the results from two 20 year simulations over the Australian region using the Weather Research and Forecasting Model and assess the results from removing all topography in the region on both mean atmospheric circulation and ECL frequency. Removing topography results in an increase in sea level pressure to the south of Australia and an increase in moisture flux convergence and rainfall near the east coast, as well as a decrease in potential vorticity to the north of the ECL region. This results in a change in the spatial distribution of cyclones, with a 37% decrease in the frequency of cyclones that develop to the south of the ECL region but a 20% increase in cyclones near the east coast. This results in little overall change in the frequency of ECLs and suggests that coarse topography is unlikely to be responsible for the difficulties in simulating coastal cyclones in global climate models
Impact of identification method on the inferred characteristics and variability of Australian east coast lows
The Australian east coast low (ECL) is both a major cause of damaging severe weather and an important contributor to rainfall and dam inflowalong the east coast, and is of interest to a wide range of groups including catchment managers and emergency services. For this reason, several studies in recent years have developed and interrogated databases of east coast lows using a variety of automated cyclone detection methods and identification criteria. This paper retunes each method so that all yield a similar event frequency within the ECL region, to enable a detailed intercomparison of the similarities, differences, and relative advantages of each method. All methods are shown to have substantial skill at identifying ECL events leading to major impacts or explosive development, but the choice of method significantly affects both the seasonal and interannual variation of detected ECL numbers. This must be taken into consideration in studies on trends or variability in ECLs, with a subcategorization of ECL events by synoptic situation of key importance
Engendering the Evidence Base: A Critical Review of the Conceptual and Empirical Foundations of Gender-Responsive Interventions for Girls’ Delinquency
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Malta (MYH9 Associated Elastin Aggregation) Syndrome: Germline Variants in MYH9 Cause Rare Sweat Duct Proliferations and Irregular Elastin Aggregations.
To the Editor.
Sweat duct proliferations and related cutaneous tumours pose a challenge for diagnosis and treatment due to the presence of multiple overlapping histopathological features (Schaller et al. 2010). In 1961 Nicolau and Balus described individuals with benign cutaneous lesions including atrophodermia vermiculata, multiple syringomata and milia which become known as Nicolau-Balus syndrome and was characterised by irregular distribution of elastin fibres (Nicolau and Balus 1961). A similar phenotype was later described as Rombo syndrome by Michaelsson et al (Michaelsson et al. 1981), with elastin distribution in these cases appearing like “swathes of steel wool” in some areas of the dermis (Van Steensel et al. 2001). In 2010, Schaller et al described several cases with the same abnormal elastin distribution, with the additional feature of sweat duct proliferations that appear morphologically similar to those found in microcystic adnexal carcinoma (MAC) patients, but (unlike MAC) were not invasive and did not require surgical resection (Schaller et al. 2010).
In this study we describe five families with clinical and histopathological features that show similarities to Nicolau-Balus and Rombo syndromes with some cases also showing MAC-like ductal proliferations (figure S1). We provide evidence that these syndromes are caused by germline pathogenic variants in MYH9. Accordingly, we propose the term MALTA (MYH9 Associated eLasTin Aggregation) syndrome to reflect the common underlying genetic basis of this disease
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