617 results match your criteria Pelizaeus-Merzbacher Disease


PLP1 Mutations in Patients with Multiple Sclerosis: Identification of a New Mutation and Potential Pathogenicity of the Mutations.

J Clin Med 2018 Oct 11;7(10). Epub 2018 Oct 11.

UQ Centre for Clinical Research, the University of Queensland, Brisbane, QLD 4029, Australia.

is located on the X-chromosome and encodes myelin proteolipid protein (PLP), the most abundant protein in central nervous system myelin. Generally, point mutations in result in X-linked dysmyelinating disorders, such as Pelizaeus-Merzbacher disease (PMD) or spastic paraplegia type 2 (SPG2). However, several case studies have identified patients with missense point mutations in and clinical symptoms and signs compatible with a diagnosis of multiple sclerosis (MS). Read More

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http://dx.doi.org/10.3390/jcm7100342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210135PMC
October 2018
6 Reads

Brain Diffusion Imaging and Tractography to Distinguish Clinical Severity of Human PLP1-Related Disorders.

Dev Neurosci 2018 27;40(4):301-311. Epub 2018 Sep 27.

Service de Neurologie Pédiatrique et Maladies Métaboliques, Centre de référence des leucodystrophies et leucoencéphalopathies de cause rare, CHU-APHP Robert-Debré, Paris, France.

Aims: We performed quantitative diffusion tensor imaging and brain tractography to distinguish clinical severity in a series of 35 patients with hypomyelinating PLP1-related disorders classified using the Motor Developmental Score according to the best motor function acquired before the age of 5 years and the gross motor function measure (GMFM) at the time of magnetic resonance imaging acquisition.

Methods: We calculated fractional anisotropy and diffusivity values in 26 regions of interest and the numbers of fibers and volumes of hemisphere tractograms. Fiber bundles on tractograms were characterized according to 3 criteria: size, direction of main-stream fibers, and connectivity of bundles (extratelencephalic projections, commissural fibers, and intrahemispheric connections). Read More

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http://dx.doi.org/10.1159/000492218DOI Listing
September 2018
1 Read
2.700 Impact Factor

Morpholino Antisense Oligomers as a Potential Therapeutic Option for the Correction of Alternative Splicing in PMD, SPG2, and HEMS.

Mol Ther Nucleic Acids 2018 Sep 5;12:420-432. Epub 2018 Jul 5.

Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address:

DNA variants of the proteolipid protein 1 gene (PLP1) that shift PLP1/DM20 alternative splicing away from the PLP1 form toward DM20 cause the allelic X-linked leukodystrophies Pelizaeus-Merzbacher disease (PMD), spastic paraplegia 2 (SPG2), and hypomyelination of early myelinating structures (HEMS). We designed a morpholino oligomer (MO-PLP) to block use of the DM20 5' splice donor site, thereby shifting alternative splicing toward the PLP1 5' splice site. Treatment of an immature oligodendrocyte cell line with MO-PLP significantly shifted alternative splicing toward PLP1 expression from the endogenous gene and from transfected human minigene splicing constructs harboring patient variants known to reduce the amount of the PLP1 spliced product. Read More

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http://dx.doi.org/10.1016/j.omtn.2018.05.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036941PMC
September 2018

Chemical Screening Identifies Enhancers of Mutant Oligodendrocyte Survival and Unmasks a Distinct Pathological Phase in Pelizaeus-Merzbacher Disease.

Stem Cell Reports 2018 Sep 23;11(3):711-726. Epub 2018 Aug 23.

Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address:

Pelizaeus-Merzbacher disease (PMD) is a fatal X-linked disorder caused by loss of myelinating oligodendrocytes and consequent hypomyelination. The underlying cellular and molecular dysfunctions are not fully defined, but therapeutic enhancement of oligodendrocyte survival could restore functional myelination in patients. Here we generated pure, scalable quantities of induced pluripotent stem cell-derived oligodendrocyte progenitor cells (OPCs) from a severe mouse model of PMD, Plp1. Read More

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http://dx.doi.org/10.1016/j.stemcr.2018.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135742PMC
September 2018
2 Reads

Clinical and mutational spectrum of Colombian patients with Pelizaeus Merzbacher Disease.

Colomb Med (Cali) 2018 Jun 30;49(2):182-187. Epub 2018 Jun 30.

Genetica Medica, Facultad de Medicina, Pontificia Universidad Javeriana. Bogotá, Colombia.

Case Presentation: Pelizaeus Merzbacher Disease (PMD) is an X-linked developmental defect of myelination that causes childhood chronic spastic encephalopathy. Its genetic etiology can be either a duplication (or other gene dosage alterations) or a punctual mutation at the locus. Clinically, it presents with developmental delay, nystagmus and, spasticity, supported by neuroimaging in which the defect of myelination is evident. Read More

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http://dx.doi.org/10.25100/cm.v49i2.2522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084915PMC
June 2018
2 Reads

Novel Mutations Identified With Next-Generation Sequencing Expand the Spectrum of PLP1-Associated Leukodystrophy Clinical Phenotypes.

Child Neurol Open 2018 23;5:2329048X18789282. Epub 2018 Jul 23.

Pediatric Motor Disorders Research Program, Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.

Next-generation sequencing was performed for 2 families with an undiagnosed neurologic disease. Analysis revealed X-linked mutations in the () gene, which is associated with X-linked Pelizaeus-Merzbacher disease and Spastic Paraplegia type 2. In family A, the novel missense mutation c. Read More

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http://dx.doi.org/10.1177/2329048X18789282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056774PMC

Protective effect of 4-Phenylbutyrate against proteolipid protein mutation-induced endoplasmic reticulum stress and oligodendroglial cell death.

Neurochem Int 2018 Sep 22;118:185-194. Epub 2018 Jun 22.

Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, France. Electronic address:

Proteolipid protein (PLP) mutation causes oligodendrocyte degeneration and myelin disorders including Pelizaeus-Merzbacher Disease (PMD). As the pathophysiological mechanisms involved in PMD are poorly known, the development of therapies remains difficult. To elucidate the pathogenic pathways, an immortalized oligodendroglial cell line (158JP) expressing PLP mutation has been generated. Read More

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http://dx.doi.org/10.1016/j.neuint.2018.06.008DOI Listing
September 2018
3 Reads

Rapid and Specific Immunomagnetic Isolation of Mouse Primary Oligodendrocytes.

J Vis Exp 2018 05 21(135). Epub 2018 May 21.

Department of Neurology and Rehabilitation, University of Illinois at Chicago;

The efficient and robust isolation and culture of primary oligodendrocytes (OLs) is a valuable tool for the in vitro study of the development of oligodendroglia as well as the biology of demyelinating diseases such as multiple sclerosis and Pelizaeus-Merzbacher-like disease (PMLD). Here, we present a simple and efficient selection method for the immunomagnetic isolation of stage three O4 preoligodendrocytes cells from neonatal mice pups. Since immature OL constitute more than 80% of the rodent-brain white matter at postnatal day 7 (P7) this isolation method not only ensures high cellular yield, but also the specific isolation of OLs already committed to the oligodendroglial lineage, decreasing the possibility of isolating contaminating cells such as astrocytes and other cells from the mouse brain. Read More

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http://dx.doi.org/10.3791/57543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101296PMC
May 2018
2 Reads

Insertion of proteolipid protein into mitochondria but not DM20 regulates metabolism of cells.

Neurosci Lett 2018 Jun 2;678:90-98. Epub 2018 May 2.

Wayne State University School of Medicine Department of Anatomy and Cell Biology, Detroit, MI, 48201, USA. Electronic address:

Proteolipid protein (PLP), besides its adhesive role in myelin, has been postulated to have multiple cellular functions. One well-documented function of PLP is regulation of oligodendrocyte (Olg) apoptosis. In contrast, DM20, an alternatively spliced product of the PLP1/Plp1 gene, has been proposed to have functions that are unique from PLP but these functions have never been elucidated. Read More

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http://dx.doi.org/10.1016/j.neulet.2018.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975245PMC
June 2018
3 Reads

Auditory function in Pelizaeus-Merzbacher disease.

J Neurol 2018 Jul 3;265(7):1580-1589. Epub 2018 May 3.

Nemours Biomedical Research, Center for Applied Clinical Genomics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.

Pelizaeus-Merzbacher disease (PMD; MIM 312080), an inherited defect of central nervous system myelin formation, affects individuals in many ways, including their hearing and language abilities. The aim of this study was to assess the auditory abilities in 18 patients with PMD by examining the functional processes along the central auditory pathways using auditory brainstem responses (ABR) and cortical auditory evoked potentials (CAEP) in response to speech sounds. The significant ABR anomalies confirm the existence of dyssynchrony previously described at the level of the brainstem in patients with PMD. Read More

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http://dx.doi.org/10.1007/s00415-018-8884-xDOI Listing
July 2018
2 Reads

Correction to: Exome sequencing reveals a novel PLP1 mutation in a Moroccan family with connatal Pelizaeus-Merzbacher disease: a case report.

BMC Pediatr 2018 04 17;18(1):138. Epub 2018 Apr 17.

Centre de Génomique Humaine, Faculté de Médecine et Pharmacie, Mohammed V University in Rabat, Rabat, Morocco.

After publication of the original article [1] it was brought to our attention that author Bouchra Ouled Amar Bencheikh was incorrectly included as Bouchra Oulad Amar Bencheikh. Read More

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http://dx.doi.org/10.1186/s12887-018-1114-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905117PMC
April 2018
3 Reads

Pelizaeus-Merzbacher disease can be a differential diagnosis in males presenting with severe neonatal respiratory distress and hypotonia.

Hum Genome Var 2018 29;5:18013. Epub 2018 Mar 29.

Division of Pediatrics, Jichi Medical University, Shimotsuke, Japan.

Pelizaeus-Merzbacher disease (PMD; MIM #312080) is a rare X-linked recessive disorder. A male neonate presented with severe respiratory distress that required tracheostomy. After the appearance of nystagmus, PMD was suspected as a diagnosis for the patient, and a missense mutation, p. Read More

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http://dx.doi.org/10.1038/hgv.2018.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874395PMC
March 2018
1 Read

Exome sequencing reveals a novel PLP1 mutation in a Moroccan family with connatal Pelizaeus-Merzbacher disease: a case report.

BMC Pediatr 2018 02 27;18(1):90. Epub 2018 Feb 27.

Centre de Génomique Humaine, Faculté de Médecine et Pharmacie, Mohammed V University in Rabat, Rabat, Morocco.

Background: Epilepsy regroups a common and diverse set of chronic neurological disorders that are characterized by spontaneous, unprovoked, and recurrent epileptic seizures. Epilepsies have a highly heterogeneous background with a strong genetic contribution and various mode of inheritance. X-linked epilepsy usually manifests as part of a syndrome or epileptic encephalopathy. Read More

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http://dx.doi.org/10.1186/s12887-018-1063-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830319PMC
February 2018
4 Reads

Neurogenetics of Pelizaeus-Merzbacher disease.

Handb Clin Neurol 2018 ;148:701-722

Center for Translational Neuromedicine and Department of Neurology, University of Rochester Medical Center, Rochester, NY, United States; Center for Translational Neuromedicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark. Electronic address:

Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder caused by mutations in the PLP1 gene, which encodes the proteolipid protein of myelinating oligodendroglia. PMD exhibits phenotypic variability that reflects its considerable genotypic heterogeneity, but all forms of the disease result in central hypomyelination associated with early neurologic dysfunction, progressive deterioration, and ultimately death. PMD has been classified into three major subtypes, according to the age of presentation: connatal PMD, classic PMD, and transitional PMD, combining features of both connatal and classic forms. Read More

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http://dx.doi.org/10.1016/B978-0-444-64076-5.00045-4DOI Listing
August 2018
1 Read

Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.

PLoS One 2018 16;13(2):e0188869. Epub 2018 Feb 16.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Objective: Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population.

Methods: 119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188869PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815574PMC
March 2018
7 Reads

[Borderline phenotype of Pelizaeus-Merzbacher disease].

Rev Neurol 2017 Dec;65(12):575-576

Hospital Regional Universitario de Malaga, Malaga, Espana.

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December 2017
1 Read

[Clinical manifestation and gene analyses of 15 patients with intellectual disability or developmental delay complicated with congenital nystagmus].

Zhonghua Er Ke Za Zhi 2017 Nov;55(11):824-829

Department of Neurology, Children's Hospital Affiliated to Capital Institute of Pediatrics, Beijing 100020, China.

To analyze the clinical and genetic features of 15 cases with intellectual disability or developmental delay (ID/DD) complicated with congenital nystagmus. The clinical characteristics and the results of laboratory tests, images and genetics of 15 patients with ID/DD complicated with congenital nystagmus, confirmed by gene diagnosis in the Department of Neurology, Children's Hospital Affiliated to Capital Institute of Pediatrics from March 2015 to October 2016, were retrospectively analyzed. The physiological function of 13 disease genes and the molecular signaling pathways were also comparatively studied. Read More

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http://dx.doi.org/10.3760/cma.j.issn.0578-1310.2017.11.007DOI Listing
November 2017
3 Reads

Oxidative stress and mitochondrial dynamics malfunction are linked in Pelizaeus-Merzbacher disease.

Brain Pathol 2018 09 26;28(5):611-630. Epub 2017 Dec 26.

Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Spain.

Pelizaeus-Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD. Read More

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http://dx.doi.org/10.1111/bpa.12571DOI Listing
September 2018
15 Reads

Mutations in RARS cause a hypomyelination disorder akin to Pelizaeus-Merzbacher disease.

Eur J Hum Genet 2017 10 26;25(10):1134-1141. Epub 2017 Jul 26.

Discipline of Paediatrics &Child Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

Pelizaeus-Merzbacher disease (PMD) is a rare Mendelian disorder characterised by central nervous system hypomyelination. PMD typically manifests in infancy or early childhood and is caused by mutations in proteolipid protein-1 (PLP1). However, variants in several other genes including gap junction protein gamma 2 (GJC2) can also cause a similar phenotype and are referred to PMD-like disease (PMLD). Read More

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http://dx.doi.org/10.1038/ejhg.2017.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602020PMC
October 2017
3 Reads

Effects of Intron 1 Sequences on Human PLP1 Expression: Implications for PLP1-Related Disorders.

Authors:
Patricia A Wight

ASN Neuro 2017 Jul-Aug;9(4):1759091417720583

1 Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Alterations in the myelin proteolipid protein gene ( PLP1) may result in rare X-linked disorders in humans such as Pelizaeus-Merzbacher disease and spastic paraplegia type 2. PLP1 expression must be tightly regulated since null mutations, as well as elevated PLP1 copy number, both lead to disease. Previous studies with Plp1-lacZ transgenic mice have demonstrated that mouse Plp1 ( mPlp1) intron 1 DNA (which accounts for slightly more than half of the gene) is required for the mPlp1 promoter to drive significant levels of reporter gene expression in brain. Read More

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http://journals.sagepub.com/doi/10.1177/1759091417720583
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http://dx.doi.org/10.1177/1759091417720583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528184PMC
December 2017
3 Reads

Different Mutations of Gap Junction Connexin 47 Lead to Discrepant Activation of Unfolded Protein Response Pathway in Pelizaeus-Merzbacher-Like Disease.

Neuropediatrics 2017 12 16;48(6):426-431. Epub 2017 Jul 16.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

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http://dx.doi.org/10.1055/s-0037-1603978DOI Listing
December 2017
12 Reads

Diseases of connexins expressed in myelinating glia.

Authors:
Charles K Abrams

Neurosci Lett 2017 May 23. Epub 2017 May 23.

Department of Neurology and Rehabilitation, College of Medicine, University of Illinois at Chicago, Chicago IL, USA. Electronic address:

Connexins are a family of integral membrane proteins most of which form gap junctions and many of which form hemichannels as well. Mutations in at least 9 of the 21 genes encoding human connexin proteins cause human diseases. Mutations in GJB1 (Cx32), expressed in both Schwann cells and oligodendrocytes, cause both a form of inherited peripheral neuropathy and a variety of CNS symptoms. Read More

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http://dx.doi.org/10.1016/j.neulet.2017.05.037DOI Listing
May 2017
6 Reads

Hypomyelinating leukodystrophy associated with a deleterious mutation in the ATRN gene.

Neurogenetics 2017 Jul 10;18(3):135-139. Epub 2017 May 10.

Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.

Hypomyelinating leukodystrophies are a group of neurodevelopmental disorders that affect proper formation of the myelin sheath in the central nervous system. They are characterized by developmental delay, hypotonia, spasticity, and variable intellectual disability. We used whole exome analysis to study the molecular basis of hypomyelinating leukodystrophy in two sibs from a consanguineous family. Read More

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http://dx.doi.org/10.1007/s10048-017-0515-7DOI Listing
July 2017
41 Reads

Modeling the Mutational and Phenotypic Landscapes of Pelizaeus-Merzbacher Disease with Human iPSC-Derived Oligodendrocytes.

Am J Hum Genet 2017 Apr 30;100(4):617-634. Epub 2017 Mar 30.

Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address:

Pelizaeus-Merzbacher disease (PMD) is a pediatric disease of myelin in the central nervous system and manifests with a wide spectrum of clinical severities. Although PMD is a rare monogenic disease, hundreds of mutations in the X-linked myelin gene proteolipid protein 1 (PLP1) have been identified in humans. Attempts to identify a common pathogenic process underlying PMD have been complicated by an incomplete understanding of PLP1 dysfunction and limited access to primary human oligodendrocytes. Read More

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http://dx.doi.org/10.1016/j.ajhg.2017.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384098PMC
April 2017
17 Reads

Efficient CNV breakpoint analysis reveals unexpected structural complexity and correlation of dosage-sensitive genes with clinical severity in genomic disorders.

Hum Mol Genet 2017 05;26(10):1927-1941

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Genomic disorders are the clinical conditions manifested by submicroscopic genomic rearrangements including copy number variants (CNVs). The CNVs can be identified by array-based comparative genomic hybridization (aCGH), the most commonly used technology for molecular diagnostics of genomic disorders. However, clinical aCGH only informs CNVs in the probe-interrogated regions. Read More

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http://dx.doi.org/10.1093/hmg/ddx102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075079PMC
May 2017
21 Reads

22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

Am J Med Genet A 2017 Apr;173(4):1066-1070

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.38109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536953PMC
April 2017
12 Reads

An Xq22.1q22.2 nullisomy in a male patient with severe neurological impairment.

Am J Med Genet A 2017 Apr;173(4):1124-1127

Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.

The proteolipid protein 1 gene (PLP1) is located on chromosome Xq22.2 and is related to X-linked recessive leukoencephalopathy (Pelizaeus-Merzbacher disease: PMD). Compared to PLP1 duplications, which are a major contributor to PMD, chromosomal deletions in this region are rare and only a few PMD patients with small deletions have been reported, suggesting that large deletions of this region would cause embryonic lethality. Read More

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http://dx.doi.org/10.1002/ajmg.a.38134DOI Listing
April 2017
4 Reads

SPG2 mimicking multiple sclerosis in a family identified using next generation sequencing.

J Neurol Sci 2017 Apr 27;375:198-202. Epub 2017 Jan 27.

Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Italy, Azienda Ospedaliera Universitaria Senese, Siena. Electronic address:

Several single gene disorders can potentially be overlooked in the differential diagnostic evaluation of patients with multiple sclerosis (MS). Pelizaeus-Merzbacher disease and spastic paraplegia type 2 are allelic X-linked disorders associated with defective myelination of the central nervous system and mutations in PLP1. Neurological symptoms are occasionally observed in female carriers of these mutations. Read More

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http://dx.doi.org/10.1016/j.jns.2017.01.069DOI Listing
April 2017
7 Reads

Cellular Pathology of Pelizaeus-Merzbacher Disease Involving Chaperones Associated with Endoplasmic Reticulum Stress.

Authors:
Ken Inoue

Front Mol Biosci 2017 24;4. Epub 2017 Feb 24.

Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry Kodaira, Japan.

Disease-causing mutations in genes encoding membrane proteins may lead to the production of aberrant polypeptides that accumulate in the endoplasmic reticulum (ER). These mutant proteins have detrimental conformational changes or misfolding events, which result in the triggering of the unfolded protein response (UPR). UPR is a cellular pathway that reduces ER stress by generally inhibiting translation, increasing ER chaperones levels, or inducing cell apoptosis in severe ER stress. Read More

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http://dx.doi.org/10.3389/fmolb.2017.00007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323380PMC
February 2017
6 Reads

Familial Case of Pelizaeus-Merzbacher Disorder Detected by Oligoarray Comparative Genomic Hybridization: Genotype-to-Phenotype Diagnosis.

Case Rep Genet 2017 4;2017:2706098. Epub 2017 Jan 4.

Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.

. Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive hypomyelinating leukodystrophy characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay. It is caused by mutation in the PLP1 gene. Read More

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http://dx.doi.org/10.1155/2017/2706098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241495PMC
January 2017
21 Reads

A novel mutation F240L identified in a patient with connatal type Pelizaeus-Merzbacher disease.

Hum Genome Var 2017 5;4:16044. Epub 2017 Jan 5.

Institute of Medical Genetics, Tokyo Women's Medical University , Tokyo, Japan.

Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive hypomyelination disorder caused by mutations in the proteolipid protein 1 gene () located on chromosome Xq22. A male patient showed severe developmental delay, pendular nystagmus and laryngeal wheezing. The auditory brain stem response showed only the first wave and brain magnetic resonance imaging showed white matter hypomyelination, suggesting typical PMD. Read More

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http://dx.doi.org/10.1038/hgv.2016.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214593PMC
January 2017
5 Reads

Endoplasmic Reticulum Protein Quality Control Failure in Myelin Disorders.

Front Mol Neurosci 2016 4;9:162. Epub 2017 Jan 4.

Biology of Myelin Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, DIBIT Milan, Italy.

Reaching the correct three-dimensional structure is crucial for the proper function of a protein. The endoplasmic reticulum (ER) is the organelle where secreted and transmembrane proteins are synthesized and folded. To guarantee high fidelity of protein synthesis and maturation in the ER, cells have evolved ER-protein quality control (ERQC) systems, which assist protein folding and promptly degrade aberrant gene products. Read More

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http://dx.doi.org/10.3389/fnmol.2016.00162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209374PMC
January 2017
2 Reads

Gene therapy targeting oligodendrocytes provides therapeutic benefit in a leukodystrophy model.

Brain 2017 03;140(3):599-616

Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics and Cyprus School of Molecular Medicine, Nicosia, Cyprus.

Pelizaeus-Merzbacher-like disease or hypomyelinating leukodystrophy-2 is an autosomal recessively inherited leukodystrophy with childhood onset resulting from mutations in the gene encoding the gap junction protein connexin 47 (Cx47, encoded by GJC2). Cx47 is expressed specifically in oligodendrocytes and is crucial for gap junctional communication throughout the central nervous system. Previous studies confirmed that a cell autonomous loss-of-function mechanism underlies hypomyelinating leukodystrophy-2 and that transgenic oligodendrocyte-specific expression of another connexin, Cx32 (GJB1), can restore gap junctions in oligodendrocytes to achieve correction of the pathology in a disease model. Read More

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http://dx.doi.org/10.1093/brain/aww351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837386PMC
March 2017
4 Reads

A genetically proven case of Pelizaeus-Merzbacher disease: Clinicoradiological clues.

Ann Indian Acad Neurol 2016 Oct-Dec;19(4):533-535

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.4103/0972-2327.194470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144486PMC
December 2016
2 Reads

Concise Review: Stem Cell-Based Treatment of Pelizaeus-Merzbacher Disease.

Stem Cells 2017 02 23;35(2):311-315. Epub 2016 Nov 23.

Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark.

Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder caused by mutation in the proteolipid protein-1 (PLP1) gene, which encodes the proteolipid protein of myelinating oligodendroglia. PMD exhibits phenotypic variability that reflects its considerable genotypic heterogeneity, but all forms of the disease result in central hypomyelination, associated in most cases with early neurological dysfunction, progressive deterioration, and ultimately death. PMD may present as a connatal, classic and transitional forms, or as the less severe spastic paraplegia type 2 and PLP-null phenotypes. Read More

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http://dx.doi.org/10.1002/stem.2530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314962PMC
February 2017
8 Reads

Lamin B1 mediated demyelination: Linking Lamins, Lipids and Leukodystrophies.

Authors:
Quasar S Padiath

Nucleus 2016 Nov;7(6):547-553

a Department of Human Genetics , Graduate School of Public Health, University of Pittsburgh , Pittsburgh , PA , USA.

Autosomal Dominant Leukodystrophy (ADLD), a fatal adult onset demyelinating disorder, is the only human disease that has been linked to mutations of the nuclear lamina protein, lamin B1, and is primarily caused by duplications of the LMNB1 gene. Why CNS myelin is specifically targeted and the mechanisms underlying ADLD are unclear. Recent work from our group has demonstrated that over expression of lamin B1 in oligodendrocytes, the myelin producing cells in the CNS, resulted in age dependent epigenetic modifications, transcriptional down-regulation of lipogenic gene expression and significant reductions of myelin-enriched lipids. Read More

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http://dx.doi.org/10.1080/19491034.2016.1260799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214339PMC
November 2016
4 Reads

A novel PLP1 mutation associated with optic nerve enlargement in two siblings with Pelizaeus-Merzbacher disease: A new MRI finding.

Brain Dev 2017 Mar 25;39(3):271-274. Epub 2016 Oct 25.

Department of Paediatric Neurology, Chelsea and Westminster NHS Foundation Trust, London, United Kingdom. Electronic address:

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked disorder characterized by hypomyelination of the Central Nervous System due to mutations in the PLP1 gene. Certain mutations of the PLP1 gene correlate with specific clinical phenotypes and neuroimaging findings. We herein report a novel mutation of the PLP1 gene in two siblings with PMD associated with a rare and protean neuroimaging finding of optic nerve enlargement. Read More

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http://dx.doi.org/10.1016/j.braindev.2016.09.012DOI Listing
March 2017
4 Reads

Corrigendum to "GJC2 promoter mutations causing Pelizaeus-Merzbacher-like disease" [Mol. Genet. Metab. 111 (2014) 393-398].

Mol Genet Metab 2016 11;119(3):293

Department of Neurology, Children's National Medical Center, Washington, DC, USA; Department of Pediatrics, Children's National Medical Center, Washington, DC, USA; Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ymgme.2016.06.011DOI Listing
November 2016
9 Reads

The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies.

Sci Rep 2016 10 25;6:35936. Epub 2016 Oct 25.

Department of Pediatrics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province, China.

Leukoencephalopathies are diseases with high clinical heterogeneity. In clinical work, it's difficult for doctors to make a definite etiological diagnosis. Here, we designed a custom probe library which contains the known pathogenic genes reported to be associated with Leukoencephalopathies, and performed targeted gene capture and massively parallel sequencing (MPS) among 49 Chinese patients who has white matter damage as the main imaging changes, and made the validation by Sanger sequencing for the probands' parents. Read More

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http://dx.doi.org/10.1038/srep35936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078786PMC
October 2016
11 Reads

Is involvement of inflammation underestimated in Pelizaeus-Merzbacher disease?

J Neurosci Res 2016 12 23;94(12):1572-1578. Epub 2016 Sep 23.

INSERM, U1127, F-75013, Paris, France.

Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating leukodystrophy resulting from proteolipid protein 1 gene (PLP1) mutations leading to oligodendrocyte loss. While neuroinflammation has recently become a common feature and actor in neurodegenerative diseases, the involvement of inflammation in PMD physiopathology is still highly debated despite evidence for strong astrogliosis and microglial cell activation. Activation of the innate immune system, and more particularly, of microglia and astrocytes, is mostly associated with the deleterious role of neuroinflammation. Read More

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http://dx.doi.org/10.1002/jnr.23931DOI Listing
December 2016
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Modeling the Chronic Loss of Optic Nerve Axons and the Effects on the Retinal Nerve Fiber Layer Structure in Primary Disorder of Myelin.

Invest Ophthalmol Vis Sci 2016 Sep;57(11):4859-4868

Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.

Purpose: We determined whether the chronic lack of optic nerve myelination and subsequent axon loss is associated with optical coherence tomography (OCT) changes in the retinal nerve fiber layer (RNFL), and whether this models what occurs in multiple sclerosis (MS) and confers its use as a surrogate marker for axon degeneration.

Methods: Using an animal model of Pelizaeus-Merzbacher disease (shp) bilateral longitudinal measurements of the peripapillary RNFL (spectral-domain OCT), electroretinograms (ERG), and visual evoked potentials (VEP) were performed in affected and control animals from 5 months to 2 years and in individual animals at single time points. Light and electron microscopy of the optic nerve and retina and histomorphometric measurements of the RNFL were compared to OCT data. Read More

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http://dx.doi.org/10.1167/iovs.16-19871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032912PMC
September 2016
4 Reads

Neurologic syndrome associated with homozygous mutation at MAG sialic acid binding site.

Ann Clin Transl Neurol 2016 08 23;3(8):650-4. Epub 2016 Jun 23.

Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland.

The MAG gene encodes myelin-associated glycoprotein (MAG), an abundant protein involved in axon-glial interactions and myelination during nerve regeneration. Several members of a consanguineous family with a clinical syndrome reminiscent of Pelizaeus-Merzbacher disease and demyelinating leukodystrophy on brain MRI were recently found to harbor a homozygous missense p.Ser133Arg MAG mutation. Read More

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http://dx.doi.org/10.1002/acn3.329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999596PMC
August 2016
12 Reads

The spectrum of leukodystrophies in children: Experience at a tertiary care centre from North India.

Ann Indian Acad Neurol 2016 Jul-Sep;19(3):332-8

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Objective: The objective of this study is to retrospectively collect and then describe the clinico-radiographical profile of confirmed cases of leukodystrophy who presented over a 5-year period to a tertiary care teaching hospital in North India.

Materials And Methods: The case records of 80 confirmed cases of leukodystrophy were reviewed and the cases have been described in terms of their clinical presentation and neuroimaging findings.

Results: The cases have been grouped into five categories: Hypomyelinating, demyelinating, disorders with vacuolization, cystic, and miscellaneous. Read More

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http://dx.doi.org/10.4103/0972-2327.179975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980955PMC
August 2016
17 Reads

A microdeletion at Xq22.2 implicates a glycine receptor GLRA4 involved in intellectual disability, behavioral problems and craniofacial anomalies.

BMC Neurol 2016 Aug 9;16:132. Epub 2016 Aug 9.

Department of Obstetrics & Gynecology, Section of Reproductive Endocrinology, Infertility & Genetics, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.

Background: Among the 21 annotated genes at Xq22.2, PLP1 is the only known gene involved in Xq22.2 microdeletion and microduplication syndromes with intellectual disability. Read More

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http://dx.doi.org/10.1186/s12883-016-0642-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979147PMC
August 2016
22 Reads

Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases.

Rare Dis 2016 22;4(1):e1198458. Epub 2016 Jun 22.

School of Biomedical Sciences and Pharmacy, The University of Newcastle , Callaghan, NSW, Australia.

We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe (-/-) xTfr2 (mut) mouse model. This was accompanied by altered expression of a group of myelin-related genes, including a suite of genes causatively linked to the rare disease family 'neurodegeneration with brain iron accumulation' (NBIA). Expanded data mining and ontological analyses have now identified additional myelin-related transcriptome changes in response to brain iron loading. Read More

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http://dx.doi.org/10.1080/21675511.2016.1198458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961263PMC
August 2016
14 Reads

Hypomyelinating Leukodystrophy due to HSPD1 Mutations: A New Patient.

Neuropediatrics 2016 Oct 12;47(5):332-5. Epub 2016 Jul 12.

Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

The hypomyelinating leukodystrophies (HMLs) encompass the X-linked Pelizaeus-Merzbacher disease (PMD) caused by PLP1 mutations and known as the classical form of HML as well as Pelizaeus-Merzbacher-like disease (PMLD) (Online Mendelian Inheritance in Man [OMIM] 608804 and OMIM 260600) due to GJC2 mutations. In addition, mutations in at least 10 other genes are known to cause HMLs. In 2008, an Israeli family with clinical and neuroimaging findings similar to those found in PMD was reported. Read More

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http://dx.doi.org/10.1055/s-0036-1584564DOI Listing
October 2016
2 Reads

General Anesthesia for a Patient With Pelizaeus-Merzbacher Disease.

Anesth Prog 2016 ;63(2):91-4

Professor, Department of Dental Anesthesiology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.

We report the successful management of general anesthesia for a patient with Pelizaeus-Merzbacher disease (PMD). PMD is one of a group of progressive, degenerative disorders of the cerebral white matter. The typical clinical manifestations of PMD include psychomotor retardation, nystagmus, abnormal muscle tone, seizures, and cognitive impairment. Read More

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http://dx.doi.org/10.2344/15-00022.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896048PMC
September 2016
2 Reads

Hypomyelinating leukodystrophies - a molecular insight into the white matter pathology.

Clin Genet 2016 10 17;90(4):293-304. Epub 2016 Jun 17.

Institute of Mother and Child, Department of Medical Genetics, Warsaw, Poland.

Hypomyelinating leukodystrophies (HLDs) are a group of neurodevelopmental disorders that affect proper formation of the myelin sheath in the central nervous system. They are characterized by developmental delay, hypotonia, spasticity, and variable intellectual disability. In the past various classification systems for HLDs have been used, based on imaging findings, clinical manifestation, and organelle-specific disorders. Read More

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http://dx.doi.org/10.1111/cge.12811DOI Listing
October 2016
1 Read