Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy

Mechanically activated (MA) ion channels convert physical forces into electrical signals. Despite the importance of this function, the involvement of mechanosensitive ion channels in human disease is poorly understood. Here we report heterozygous missense mutations in the gene encoding the MA ion channel TMEM63A that result in an infantile disorder resembling a hypomyelinating leukodystrophy. Four unrelated individuals presented with congenital nystagmus, motor delay, and deficient myelination on serial scans in infancy, prompting the diagnosis of Pelizaeus-Merzbacher (like) disease.
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Report Source Type: research

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ConclusionThe clinical and imaging findings of patients withPOLR1C hypomyelinating leukodystrophy are reviewed. Interestingly, severe myoclonic dystonia and T2 hypointensity of the substantia nigra and the subthalamic nucleus are not reported yet and could be helpful for the diagnosis ofPOLR1C hypomyelinating leukodystrophy.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
Publication date: Available online 3 December 2018Source: Multiple Sclerosis and Related DisordersAuthor(s): Ji Zhou, Xiaopeng Lu, Yao Zhang, Taoyun Ji, Yiwen Jin, Min Xu, Xinhua Bao, Yuehua Zhang, Hui Xiong, Xingzhi Chang, Yuwu Jiang, Ye WuABSTRACTBackgroundSome studies have reported clinical features of relapsing MOG-IgG-associated CNS demyelination principally in Caucasians children. It is not clear whether Chinese children share the same phenotype.ObjectiveTo delineate the clinical characteristics in Chinese children with relapsing MOG-IgG-associated demyelination.MethodsA follow-up study on 23 Children with relapsing ...
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
ConclusionsGlobal reduction of grey matter glucose metabolism in this white matter disease most likely depends on a combination of cortical afferent dysfunction and, in later stages, neuronal loss. The lowest metabolism in the cerebellum is consistent with histopathological findings and prominent cerebellar symptoms.
Source: Acta Neurologica Scandinavica - Category: Neurology Authors: Tags: ORIGINAL ARTICLE Source Type: research
To the Editor Recently, Wu et al reported the case of an adult patient with late-onset cobalamin C disease who received an incorrect diagnosis of adult metachromatic leukodystrophy (MLD). In this patient, the disease onset was characterized by acute psychiatric symptoms and spastic paraparesis. A brain magnetic resonance imagining (MRI) scan performed 2 months after the onset showed an area of hyperintensity on fluid-attenuated inversion recovery images in the right occipital subcortical white matter. The involvement of bilateral occipital white matter and centrum semiovale was evident at a follow-up MRI that was performed...
Source: JAMA Neurology - Category: Neurology Source Type: research
CONCLUSIONSClinical evidence and stability of advanced MR measures related to myelin and axons supports HSCT as an effective treatment strategy for stopping progression associated with late‐onset Krabbe disease.
Source: Journal of Neuroimaging - Category: Radiology Authors: Tags: Short Communication Source Type: research
In conclusion, imaging at 3T identified additional features in 4H leukodystrophy, aiding the MRI diagnosis of this entity. [...] Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Neuropediatrics - Category: Neurology Authors: Tags: Original Article Source Type: research
The Rojas family at a recent visit to Boston Children’s. When Paul and Liliana Rojas talk about their life, they describe it in one of two ways — the way it was before their sons, 10-year-old Brandon and 7-year-old Brian, were diagnosed with ALD, and the way it is after. Their story is one of heartbreak — but also hope, in the form of a new clinical trial. Learn more about the results of the clinical trial, recently published in the New England Journal of Medicine, that halted the progression of Brian’s ALD. ALD is short for adrenoleukodystrophy, a debilitating brain disease that simply goes by...
Source: Thrive, Children's Hospital Boston - Category: Pediatrics Authors: Tags: Diseases & Conditions Our Patients’ Stories Research and Innovation adrenoleukodystrophy ALD clinical trial Dana-Farber/Boston Children's Cancer and Blood Disorders Center David Williams MD gene therapy Lorenzo's Oil New England Jour Source Type: news
Conclusions:Exome sequencing can provide definitive diagnosis in cases presenting with rare genetic disease and should be considered in the routine genetic evaluation of the patients presenting with adult- and/or sporadic-onset progressive cerebellar ataxia for which no other cause can be identified.Study Supported by:This study was supported by NIH R01-NS082094 (BLF).Disclosure: Dr. Arac has nothing to disclose. Dr. Olney has nothing to disclose. Dr. Fogel has nothing to disclose.
Source: Neurology - Category: Neurology Authors: Tags: General Neurology: The Eyes Have It and White Matter Matters Source Type: research
Neuropediatrics DOI: 10.1055/s-0037-15991414H (hypomyelination, hypodontia and hypogonadotropic hypogonadism) leukodystrophy (4H) is an autosomal recessive hypomyelinating white matter (WM) disorder with neurologic, dental, and endocrine abnormalities. The aim of this study was to develop and validate a magnetic resonance imaging (MRI) scoring system for 4H. A scoring system (0–54) was developed to quantify hypomyelination and atrophy of different brain regions. Pons diameter and bicaudate ratio were included as measures of cerebral and brainstem atrophy, and reference values were determined using controls. Five inde...
Source: Neuropediatrics - Category: Neurology Authors: Tags: Original Article Source Type: research
We present here a case of pachygyria who presented to us with some atypical features including "tigroid-like stripes" and "leopard-like pattern" on MRI brain which has not been reported in the medical literature previously.
Source: Journal of Clinical Imaging Science - Category: Radiology Authors: Source Type: research
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