Compound heterozygous mutations in SNAP29 is associated with Pelizaeus-Merzbacher-like disorder (PMLD)

AbstractPelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukodystrophy, which is clinically and radiologically similar to X-linked Pelizaeus-Merzbacher disease (PMD). PMLD is characterized by early-onset nystagmus, delayed development (motor delay, speech delay and dysarthria), dystonia, hypotonia typically evolving into spasticity, ataxia, seizures, optic atrophy, and diffuse leukodystrophy on magnetic resonance imaging (MRI). We identified a 12-year-old Caucasian/Hispanic male with the classical clinical characteristics of PMLD with lack of myelination of the subcortical white matter, and absence of the splenium of corpus callosum. Exome sequencing in the trio revealed novel compound heterozygous pathogenic mutations inSNAP29 (p.Leu119AlafsX15, c.354DupG and p.0?, c.2T  >  C). Quantitative analysis of the patient’s blood cells through RNA sequencing identified a significant decrease inSNAP29 mRNA expression, while western blot analysis on fibroblast cells revealed a lack of protein expression compared to parental and control cells. Mutations inSNAP29 have previously been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome. Typical skin features described in CEDNIK syndrome, such as generalized ichthyosis and keratoderma, were absent in our patient. Moreover, the early onset nystagmus and leukodystrophy were consistent with a PMLD diagnosis. These findings suggest that loss o...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research

Related Links:

This article and accompanying video show the technique and discusses the technical pearls of a latissimus tendon repair using suture button fixation via a single-incision approach.
Source: Arthroscopy Techniques - Category: Surgery Source Type: research
Conclusion: Our findings implicate areas previously reported to be involved in OCD, as well as areas not typically implicated in OCD, suggesting that the neurobiological profile of TS+OCD is intermediate to pure TS and pure OCD.
Source: NeuroImage: Clinical - Category: Radiology Source Type: research
Publication date: February 2020Source: IJC Heart &Vasculature, Volume 26Author(s): Marthe A.J. Becker, Cornelis P. Allaart, Alwin Zweerink, Jan H. Cornel, Peter M. van de Ven, Albert C. van Rossum, Tjeerd GermansAbstractBackgroundSeptal midwall late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is a characteristic finding in nonischemic dilated cardiomyopathy (DCM) and is associated with adverse cardiac events. QRS-prolongation in DCM is also frequently present and a predictor of arrhythmic events and mortality. Since the His-Purkinje fibres are located in the interventricular septum, QRS-pro...
Source: IJC Heart and Vasculature - Category: Cardiology Source Type: research
Conclusions: Introducing pre-biopsy mpMRI into our contemporary PCa diagnosis pathway increased the diagnostic yield of transrectal biopsy by increasing the prostate cancer detection. This enabled the introduction of clinically significant prostate cancer (csPCa) treatment. mpMRI application also allowed biopsy to be avoided among patients with no csPCa. PMID: 31969912 [PubMed]
Source: Journal of Contemporary Brachytherapy - Category: Cancer & Oncology Tags: J Contemp Brachytherapy Source Type: research
CONCLUSIONS: Higher CAC scores were associated with higher odds of lacunar infarction, DSWMH, and ICAS. The presence and degree of CAC may be a useful indicator for SCVDs involving small and large vessels. PMID: 31969522 [PubMed - as supplied by publisher]
Source: Journal of Atherosclerosis and Thrombosis - Category: Cardiology Tags: J Atheroscler Thromb Source Type: research
Publication date: Available online 25 January 2020Source: MethodsAuthor(s): Alan P. Benson, Harley J. Stevenson-Cocks, Dominic G. Whittaker, Ed White, Michael A. ColmanAbstractComputational models of the heart, from cell-level models, through one-, two- and three-dimensional tissue-level simplifications, to biophysically-detailed three-dimensional models of the ventricles, atria or whole heart, allow the simulation of excitation and propagation of this excitation, and have provided remarkable insight into the normal and pathological functioning of the heart. In this article we present equations for modelling cellular excit...
Source: Methods - Category: Molecular Biology Source Type: research
Publication date: Available online 23 January 2020Source: Mutation Research/Fundamental and Molecular Mechanisms of MutagenesisAuthor(s): Kalyan Mahapatra, Sujit RoyAbstractBecause of their sessile lifestyle, plants are inescapably exposed to various kinds of environmental stresses throughout their lifetime. Therefore, to regulate their growth and development, plants constantly monitor the environmental signals and respond appropriately. However, these environmental stress factors, along with some endogenous metabolites, generated in response to environmental stress factors often induce various forms of DNA damage in plant...
Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - Category: Cytology Source Type: research
Publication date: Available online 23 January 2020Source: NeuroImageAuthor(s): Jacob-Jan Sloots, Geert Jan Biessels, Jaco J.M. ZwanenburgAbstractMicrovascular blood volume pulsations due to the cardiac and respiratory cycles induce brain tissue deformation and, as such, are considered to drive the brain's waste clearance system. We have developed a high-field magnetic resonance imaging (MRI) technique to quantify both cardiac and respiration-induced tissue deformations, which could not be assessed noninvasively before. The technique acquires motion encoded snapshot images in which various forms of motion and confounders ar...
Source: NeuroImage - Category: Neuroscience Source Type: research
AbstractBackground and ObjectiveSecukinumab, an anti-interleukin (IL)-17A monoclonal antibody, has demonstrated low radiographic progression over 4  years in patients with ankylosing spondylitis (AS). An adalimumab (tumor necrosis factor [TNF] inhibitor) biosimilar, GP2017 (SDZ-ADL; Sandoz), has been approved by the European Medicines Agency (July 2018) for use in all same indications as adalimumab, including AS. Adalimumab has also shown low long-term radiographic progression in patients with AS. Direct comparison of radiographic progression in AS between IL-17A and TNF inhibitors has not been studied. SURPASS is the...
Source: Clinical Drug Investigation - Category: Drugs & Pharmacology Source Type: research
We present a young female patient (36 years) admitted to Department of Ophthalmology due to visual loss on the left eye. Magnetic resonance imaging showed demyelinating lesions in frontal and parietal lobe, periventricularly, in mesencephalon and right cerebellar hemisphere, and left optic neuritis; magnetic resonance angiography was normal. The patient's history revealed renal dysfunction, hypothyroidism, and miscarriage in the 6th month of pregnancy due to eclampsia, and Fabry disease in family (mother and two sisters). She was transferred to the Department of Neurology for further evaluation of the demyelinating disorde...
Source: Acta Clinica Croatica - Category: General Medicine Tags: Acta Clin Croat Source Type: research
More News: Ataxia | Brain | Dystonia | Genetics | Ichthyosis | Leukodystrophies | MRI Scan | Neurology | Skin | Study