A Review of Copy Number Variants in Inherited Neuropathies.

A Review of Copy Number Variants in Inherited Neuropathies. Curr Genomics. 2018 Sep;19(6):412-419 Authors: Salpietro V, Manole A, Efthymiou S, Houlden H Abstract The rapid development in the last 10-15 years of microarray technologies, such as oligonucleotide array Comparative Genomic Hybridization (CGH) and Single Nucleotide Polymorphisms (SNP) genotyping array, has improved the identification of fine chromosomal structural variants, ranging in length from kilobases (kb) to megabases (Mb), as an important cause of genetic differences among healthy individuals and also as disease-susceptibility and/or disease-causing factors. Structural genomic variations due to unbalanced chromosomal rearrangements are known as Copy-Number Variants (CNVs) and these include variably sized deletions, duplications, triplications and translocations. CNVs can significantly contribute to human diseases and rearrangements in several dosage-sensitive genes have been identified as an important causative mechanism in the molecular aetiology of Charcot-Marie-Tooth (CMT) disease and of several CMT-related disorders, a group of inherited neuropathies with a broad range of clinical phenotypes, inheritance patterns and causative genes. Duplications or deletions of the dosage-sensitive gene PMP22 mapped to chromosome 17p12 represent the most frequent causes of CMT type 1A and Hereditary Neuropathy with liability to Pressure Palsies (HNPP), respectively. Additionally, CNVs have been iden...
Source: Current Genomics - Category: Genetics & Stem Cells Tags: Curr Genomics Source Type: research

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Yamaguchi M Abstract Mitochondrial dysfunction causes various diseases. Mutations in the SLC25A46 gene have been identified in mitochondrial diseases that are sometimes classified as Charcot-Marie-Tooth disease type 2, optic atrophy, and Leigh syndrome. A homolog of SLC25A46 was identified in Drosophila and designated as dSLC25A46 (CG5755). We previously established mitochondrial disease model targeting of dSLC25A46, which causes locomotive dysfunction and morphological defects at neuromuscular junctions, such as reduced synaptic branch lengths and decreased numbers of boutons. The diverse symptoms of mitochondria...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
Patient-tailored RNA interference prevents the onset of Charcot-Marie-Tooth 2D disease.
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Editors ' Choice Source Type: research
by Carmichael F. Ong, Thomas Geijtenbeek, Jennifer L. Hicks, Scott L. Delp Deficits in the ankle plantarflexor muscles, such as weakness and contracture, occur commonly in conditions such as cerebral palsy, stroke, muscular dystrophy, Charcot-Marie-Tooth disease, and sarcopenia. While these deficits likely contribute to observed gait pathologies, determining cause-effect relationships is difficult due to the often co-occurring biomechanical and neural deficits. To elucidate the effects of weakness and contracture, we systematically introduced isolated deficits into a musculoskeletal model and generated simulations of walk...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research
Charcot-Marie-Tooth disease (CMT) is a rare hereditary peripheral neuropathy. Its sensorimotor clinical manifestations are heterogeneous, and it might also influence cognitive functions. Physical activity is recommended for adults with CMT, however there is a lack of studies focusing on the effects of physical activity in children with CMT. Dance practice is beneficial for motor and cognitive functions. Adapted dance is interesting for children with CMT because it could address the functional deficits.
Source: Journal of Bodywork and Movement Therapies - Category: Physiotherapy Authors: Source Type: research
Abstract Structural variation in the human genome has emerged as a major cause of disease as genomic data have accumulated. One of the most common structural variants associated with human disease causes the heritable neuropathy known as Charcot-Marie-Tooth (CMT) disease type 1A. This 1.4 Mb duplication causes nearly half of the CMT cases that are genetically diagnosed. The PMP22 gene is highly induced in Schwann cells during development, although its precise role in myelin formation and homeostasis is still under active investigation. The PMP22 gene can be considered as a nucleoprotein complex with enzymatic acti...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research
Contributors : Sven Bervoets ; Na Wei ; Maria-Luise Erfurth ; Shazie Yusein-Myashkova ; Biljana Ermanoska ; Ligia Mateiu ; Bob Asselbergh ; David Bloquel ; Priyanka Kakad ; Tyrone Penserga ; Florian P Thomas ; Velina Guergueltcheva ; Ivailo Tournev ; Tanja Godenschwege ; Albena Jordanova ; Xiang-Lei YangSeries Type : Expression profiling by high throughput sequencingOrganism : Drosophila melanogasterCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, bu...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Drosophila melanogaster Source Type: research
We report a new family with two affected individuals. The proband presented with slight early developmental delay and clumsiness. At 3y6m, he experienced a tonic-clonic seizure that later evolved into intractable epilepsy. Progressive regression of intellect and motor skills, and disturbed behavior were evident since 8-9y.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
In 2016, MORC2 was added to the list of genes associated with axonal Charcot-Marie-Tooth disease, CMT2Z. Most CMT2Z patients develop symptoms of motor and sensory neuropathy in childhood or early adulthood with additional features like intellectual disability, cranial nerve involvement and seizures. In addition to the MORC2 hotspot mutation p.R190W, several familial mutations have been described. A distinct infantile-onset phenotype due to de novo MORC2 mutations has been described so far in six CMT2Z patients.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
We report two unrelated CMT1D patients seen at the Dubowitz Neuromuscular Centre in London, sharing a heterozygous dominant EGR2 variant.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Spinal muscular atrophy (SMA 5q) is one of the most frequent autosomal recessive disease in childhood and is caused by mutations of SMN1 gene. SMA patients present with progressive muscle weakness and atrophy. SMA coexisting with another genetic entity is extremely rare and remains a diagnostic challenge. So-called "double trouble" cases demand special approach and individual multidisciplinary management. Here, we present two new cases of SMA overlapping with hereditary spastic paraplegia or Noonan syndrome, and follow-up of our previously reported patient with SMA and Charcot-Marie-Tooth 1A.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
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