678 results match your criteria Pelizaeus-Merzbacher Disease


The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data.

Front Pediatr 2021 13;9:633385. Epub 2021 May 13.

Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

Leukodystrophies (LDs) are inherited heterogeneous conditions that affect the central nervous system with or without peripheral nerve involvement. They are individually rare, but collectively, they are common. Thirty disorders were included by the Global Leukodystrophy Initiative Consortium (GLIA) as LDs. Read More

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Recent Advancements in the Diagnosis and Treatment of Leukodystrophies.

Semin Pediatr Neurol 2021 Apr 10;37:100876. Epub 2021 Feb 10.

Division of Neurology, Nationwide Children's Hospital, Columbus, OH. Electronic address:

Leukodystrophies and genetic leukoencephalopathies comprise a growing group of inherited white matter disorders. Diagnostic rates have improved with increased utilization of next generation sequencing. As treatment options continue to advance for leukodystrophies, so will candidacy for inclusion in the United States' newborn Recommended Universal Screening Panel as was achieved for X-linked adrenoleukodystrophy. Read More

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Investigating oligodendrocyte connexins: Heteromeric interactions between Cx32 and mutant or wild-type forms of Cx47 do not contribute to or modulate gap junction function.

Glia 2021 Aug 9;69(8):1882-1896. Epub 2021 Apr 9.

Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA.

Oligodendrocytes express two gap junction forming connexins, connexin 32 (Cx32) and Cx47; therefore, formation of heteromeric channels containing both Cx47 and Cx32 monomers might occur. Mutations in Cx47 cause both Pelizaeus-Merzbacher-like disease Type 1 (PMLD1) and hereditary spastic paraparesis Type 44 (SPG44) and heteromer formation between these mutants and Cx32 may contribute to the pathogenesis of these disorders. Here, we utilized electrophysiological and antibody-based techniques to examine this possibility. Read More

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Hypomyelinating Leukodystrophy 15 (HLD15)-Associated Mutation of EPRS1 Leads to Its Polymeric Aggregation in Rab7-Positive Vesicle Structures, Inhibiting Oligodendroglial Cell Morphological Differentiation.

Polymers (Basel) 2021 Mar 29;13(7). Epub 2021 Mar 29.

Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.

Pelizaeus-Merzbacher disease (PMD), also known as hypomyelinating leukodystrophy 1 (HLD1), is an X-linked recessive disease affecting in the central nervous system (CNS). The gene responsible for HLD1 encodes proteolipid protein 1 (plp1), which is the major myelin structural protein produced by oligodendroglial cells (oligodendrocytes). HLD15 is an autosomal recessive disease affecting the glutamyl-prolyl-aminoacyl-tRNA synthetase 1 () gene, whose product, the EPRS1 protein, is a bifunctional aminoacyl-tRNA synthetase that is localized throughout cell bodies and that catalyzes the aminoacylation of glutamic acid and proline tRNA species. Read More

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Deep intronic deletion in intron 3 of PLP1 is associated with a severe phenotype of Pelizaeus-Merzbacher disease.

Hum Genome Var 2021 Apr 1;8(1):14. Epub 2021 Apr 1.

Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.

Recently, altered PLP1 splicing was confirmed as a genetic cause of hypomyelination of early myelinating structures (HEMS). A novel deep intronic deletion in intron 3 of PLP1 (NM_000533.5: c. Read More

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Spinal cord involvement and paroxysmal events in "Infantile Onset Transient Hypomyelination" due to TMEM63A mutation.

J Hum Genet 2021 Mar 30. Epub 2021 Mar 30.

COALA (Center for diagnosis and treatment of leukodystrophies), V. Buzzi Children's Hospital, Milano, Italy.

Monoallelic mutations on TMEM63A have been recently reported as cause of a previously unrecognized disorder named "infantile-onset transient hypomyelination". Clinical and neuroradiological presentation is described as highly similar to Pelizaeus-Merzbacher Disease but evolution over time was surprisingly benign with a progressive spontaneous improving course. We report on a new TMEM63A-mutated girl. Read More

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One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2.

Stem Cell Reports 2021 Apr 25;16(4):771-783. Epub 2021 Mar 25.

Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany. Electronic address:

Limited access to human oligodendrocytes impairs better understanding of oligodendrocyte pathology in myelin diseases. Here, we describe a method to robustly convert human fibroblasts directly into oligodendrocyte-like cells (dc-hiOLs), which allows evaluation of remyelination-promoting compounds and disease modeling. Ectopic expression of SOX10, OLIG2, and NKX6. Read More

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Novel Mutations in NPC1 are Associated with Pelizaeus-Merzbacher-Like Disease: A Case Report.

Int J Gen Med 2021 9;14:797-803. Epub 2021 Mar 9.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukodystrophy with clinical symptoms and imaging manifestations similar to those of Pelizaeus-Merzbacher disease (PMD), an X-linked recessive hypomyelinating leukodystrophy. Typical manifestations of PMLD are nystagmus, dysmyotonia, ataxia, progressive motor dysfunction, and diffuse leukodystrophy on magnetic resonance imaging (MRI). This report identified novel mutations in NCP1 causing PMLD. Read More

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-related Neurodevelopmental Disorder With Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Mimics Pelizaeus-Merzbacher Disease.

Neurol Genet 2021 Feb 17;7(1):e539. Epub 2020 Dec 17.

Division of Neurology and Developmental Neuroscience (D.G.C., D.T., L.F., K.P., L.T.E., H.-T.C.), Department of Pediatrics, BCM, Houston, TX; Texas Children's Hospital (D.G.C., D.T., L.F., K.P., L.T.E., H.-T.C.), Houston, TX; Department of Neurology and Neurotherapeutics (M.H.), UTSW, Dallas, TX; Department of Molecular and Human Genetics (L.T.E., H.-T.C.), BCM, Houston, TX; Department of Neuroscience (H.-T.C.), BCM, Houston, TX; Program in Development (H.-T.C.), Disease Models, and Therapeutics, BCM, Houston, TX; McNair Medical Institute (H.-T.C.), The Robert and Janice McNair Foundation, Houston, TX; and Jan and Dan Duncan Neurological Research Institute (H.-T.C.), Texas Children's Hospital, Houston, TX.

Objective: To demonstrate that de novo missense single nucleotide variants (SNVs) in cause a neurodevelopmental disorder with leukoencephalopathy resembling Pelizaeus-Merzbacher disease (PMD).

Methods: A retrospective chart review was performed of 2 unrelated males evaluated at a single institution with de novo SNVs identified by clinical exome sequencing (ES). Clinical and radiographic data were reviewed and summarized. Read More

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February 2021

Genetic testing of leukodystrophies unraveling extensive heterogeneity in a large cohort and report of five common diseases and 38 novel variants.

Sci Rep 2021 Feb 5;11(1):3231. Epub 2021 Feb 5.

Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

This study evaluates the genetic spectrum of leukodystrophies and leukoencephalopathies in Iran. 152 children, aged from 1 day to 15 years, were genetically tested for leukodystrophies and leukoencephalopathies based on clinical and neuroradiological findings from 2016 to 2019. Patients with a suggestive specific leukodystrophy, e. Read More

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February 2021

Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease.

Sci China Life Sci 2021 Jan 28. Epub 2021 Jan 28.

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.

Mutations of the genes encoding aminoacyl-tRNA synthetases are highly associated with various central nervous system disorders. Recurrent mutations, including c.5A>G, p. Read More

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January 2021

Expanding the Clinical and Mutational Spectrum of the -Related Hypomyelination of Early Myelinated Structures (HEMS).

Brain Sci 2021 Jan 13;11(1). Epub 2021 Jan 13.

Unit of Neuromuscular and Neurodegenerative Diseases, Department of Neuroscience, IRCCS Bambino Gesù Children's Hospital, 00146 Rome, Italy.

The gene, located on chromosome Xq22, encodes the proteolipid protein 1 and its isoform DM20. Mutations in cause a spectrum of white matter disorders of variable severity. Here we report on four additional HEMS patients from three families harboring three novel mutations in exon 3B detected by targeted next-generation sequencing. Read More

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January 2021

Prenatal diagnosis of duplication by single nucleotide polymorphism array in a family with Pelizaeus-Merzbacher disease.

Aging (Albany NY) 2021 01 11;13(1):1488-1497. Epub 2021 Jan 11.

Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Gulou, Fuzhou 350001, Fujian Province, China.

A family with a history of Pelizaeus-Merzbacher disease (PMD) received prenatal diagnosis of gene duplication in a fetus using a single nucleotide polymorphism (SNP) array. A 27-year-old pregnant woman was referred for genetic counseling due to her four-year-old son being diagnosed with a suspected classic type of PMD. Amniocentesis was performed at 18 and 3/7 weeks of gestation, and the SNP array was carried out on DNA from the mother, her affected son, and fetus, then further confirmed by multiplex ligation-dependent probe amplification (MLPA). Read More

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January 2021

Induced pluripotent stem cells established from a female patient with Xq22 deletion confirm that BEX2 escapes from X-chromosome inactivation.

Congenit Anom (Kyoto) 2021 Mar 13;61(2):63-67. Epub 2020 Dec 13.

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

Large deletions in Xq22 are responsible for neurodevelopmental disorders, including severe intellectual disability and behavioral abnormalities. Although the deletion regions contain PLP1, the gene related to Pelizaeus-Merzbacher disease (PMD), patients with Xq22 deletions show no clinical features of PMD such as paraplegia and white matter abnormalities. This could be due to skewed X-chromosome inactivation (XCI) occurring predominantly in the affected allele. Read More

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Functional characterization of Polr3a hypomyelinating leukodystrophy mutations in the S. cerevisiae homolog, RPC160.

Gene 2021 Feb 22;768:145259. Epub 2020 Oct 22.

Departments of Biochemistry and Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Mutations in RNA polymerase III (Pol III) cause hypomeylinating leukodystrophy (HLD) and neurodegeneration in humans. POLR3A and POLR3B, the two largest Pol III subunits, together form the catalytic center and carry the majority of disease alleles. Disease-causing mutations include invariant and highly conserved residues that are predicted to negatively affect Pol III activity and decrease transcriptional output. Read More

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February 2021

[Analysis of genomic copy number variants in a patient with congenital type Pelizaeus-Merzbacher disease].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Oct;37(10):1150-1153

Department of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, China.

Objective: To explore the genotypic and phenotypic characteristics of a child with congenital Pelizaeus-Merzbacher disease.

Methods: Clinical, imaging and genetic characteristics of the child were retrospectively analyzed.

Results: The patient manifested significantly reduced muscle tension, apparent tremor of eyeballs, and retardation of motor development after birth. Read More

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October 2020

Anaphylactic Reaction to Tranexamic Acid During Posterior Spinal Fusion: A Case Report.

JBJS Case Connect 2020 Jul-Sep;10(3):e2000130

1Department of Orthopaedics and Rehabilitation, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico.

Case: We present a 20-year-old man who suffered anaphylactic shock during posterior spinal fusion for neuromuscular scoliosis with the offending agent later identified via intradermal testing to be tranexamic acid (TXA).

Conclusion: TXA, although an increasingly common drug, can be the cause of sudden anaphylactic shock intraoperatively. This now represents the fifth reported case in the literature of patients ranging from 15 years to 80 years old with no previous exposure to the drug. Read More

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Expression of kinase-deficient MEK2 ameliorates Pelizaeus-Merzbacher disease phenotypes in mice.

Biochem Biophys Res Commun 2020 10 13;531(4):445-451. Epub 2020 Aug 13.

Laboratory of Molecular Neuroscience and Neurology, Hachioji, Tokyo, 192-0392, Japan; Laboratory of Molecular Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo, 157-8535, Japan. Electronic address:

Pelizaeus-Merzbacher disease (PMD) is characterized as a congenital hypomyelinating disorder in oligodendrocytes, myelin-forming glial cells in the central nervous system (CNS). The responsible gene of PMD is plp1, whose multiplication, deletion, or mutation is associated with PMD. We previously reported that primary oligodendrocytes overexpressing proteolipid protein 1 (PLP1) do not have the ability to differentiate morphologically, whereas inhibition of mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) by its cognate siRNA or chemical inhibitor reverses their undifferentiated phenotypes. Read More

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October 2020

Suppression of proteolipid protein rescues Pelizaeus-Merzbacher disease.

Nature 2020 09 1;585(7825):397-403. Epub 2020 Jul 1.

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

Mutations in PLP1, the gene that encodes proteolipid protein (PLP), result in failure of myelination and neurological dysfunction in the X-chromosome-linked leukodystrophy Pelizaeus-Merzbacher disease (PMD). Most PLP1 mutations, including point mutations and supernumerary copy variants, lead to severe and fatal disease. Patients who lack PLP1 expression, and Plp1-null mice, can display comparatively mild phenotypes, suggesting that PLP1 suppression might provide a general therapeutic strategy for PMD. Read More

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September 2020

A recurrent TMEM106B mutation in hypomyelinating leukodystrophy: A rapid diagnostic assay.

Brain Dev 2020 Sep 25;42(8):603-606. Epub 2020 Jun 25.

Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Introduction: Hypomyelinating leukodystrophies (HLDs) are genetically heterogeneous syndromes, presenting abnormalities in myelin development in the central nervous system. Recently, a recurrent de novo mutation in TMEM106B was identified to be responsible for five cases of HLD. We report the first Japanese case of TMEM106B gene mutation. Read More

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September 2020

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing.

Am J Med Genet A 2020 08 23;182(8):1906-1912. Epub 2020 Jun 23.

Department of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. Read More

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Rehabilitative management of an infant with Pelizaeus-Merzbacher disease: A case report.

Medicine (Baltimore) 2020 May;99(22):e20110

Department of Physical & Rehabilitation Medicine, Chonnam National University Medical School & Hospital, Gwangju City, Republic of Korea.

Rationale: Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive trait and a rare disease characterized by abnormal myelin formation in the central nervous system. Since Pelizaeus and Merzbacher reported the pathology of PMD in the 1990s most studies have examined pharmacological treatments. No studies have reported the effects of rehabilitation on patients with PMD aimed at improving their functional abilities. Read More

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Generation of a human iPSC line (MPIi006-A) from a patient with Pelizaeus-Merzbacher disease.

Stem Cell Res 2020 07 7;46:101839. Epub 2020 May 7.

Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, Münster 48149, Germany; Medical Faculty, University of Münster, Domagkstrasse 3, Münster 48149, Germany. Electronic address:

We established a human induced pluripotent stem cells (hiPSC) line (MPIi006-A) from fibroblasts of a 20-year-old male Pelizaeus-Merzbacher disease (PMD) patient with a hemizygous 643C>T mutation in proteolipid protein 1 (PLP1) gene using a retroviral delivery of OCT4, SOX2, KLF4 and c-MYC. The MPIi006-A iPSC line carried the mutation, displayed typical iPSC morphology, expressed pluripotent stem cell makers, exhibited normal karyotype and were capable of differentiating into cells representative of three germ layers. Read More

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Neural stem cells restore myelin in a demyelinating model of Pelizaeus-Merzbacher disease.

Brain 2020 05;143(5):1383-1399

School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.

Pelizaeus-Merzbacher disease is a fatal X-linked leukodystrophy caused by mutations in the PLP1 gene, which is expressed in the CNS by oligodendrocytes. Disease onset, symptoms and mortality span a broad spectrum depending on the nature of the mutation and thus the degree of CNS hypomyelination. In the absence of an effective treatment, direct cell transplantation into the CNS to restore myelin has been tested in animal models of severe forms of the disease with failure of developmental myelination, and more recently, in severely affected patients with early disease onset due to point mutations in the PLP1 gene, and absence of myelin by MRI. Read More

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Generation of the human induced pluripotent stem cell line (ZJUi005-A) from a patient with Pelizaeus-Merzbacher disease (PMD) carrying a novel hemizygous mutation in PLP1 gene.

Stem Cell Res 2020 05 19;45:101791. Epub 2020 Apr 19.

Department of Reproductive Genetics, Women's Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China. Electronic address:

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked leukodystrophy caused by mutations in the proteolipid protein 1 gene (PLP1) which is specifically expressed on the myelin sheath of oligodendrocytes. We established an induced pluripotent stem cell (iPSC) line (ZJUi005-A) from peripheral blood mononuclear cells of an 18-year-old male PMD patient with a novel hemizygous c.437T>C mutation in PLP1 gene using episomal reprogramming plasmids. Read More

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Epilepsy in children with leukodystrophies.

J Neurol 2020 Sep 9;267(9):2612-2618. Epub 2020 May 9.

Department of Pediatrics, Peking University First Hospital, No. 1 Xi'an Men Street, West District, Beijing, 100034, China.

Background: Epilepsy might be one of the manifestations in children with leukodystrophies, but the incidence of epilepsy in different types of leukodystrophies is unclear yet.

Methods: A retrospective observational cohort study was performed on children diagnosed with leukodystrophies in Peking University First Hospital from January 2004 to June 2019, and the patients were followed for 5.5 years (0. Read More

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September 2020

PP1C and PP2A are p70S6K Phosphatases Whose Inhibition Ameliorates HLD12-Associated Inhibition of Oligodendroglial Cell Morphological Differentiation.

Biomedicines 2020 Apr 16;8(4). Epub 2020 Apr 16.

Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.

Myelin sheaths created by oligodendroglial cells encase neuronal axons to achieve saltatory conduction and protect axons. Pelizaeus-Merzbacher disease (PMD) is a prototypic, hereditary demyelinating oligodendroglial disease of the central nervous system (CNS), and is currently known as hypomyelinating leukodystrophy 1 (HLD1). HLD12 is an autosomal recessive disorder responsible for the gene that encodes vacuolar protein sorting-associated protein 11 homolog (VPS11). Read More

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Clinical and genetic aspects of hereditary spastic paraplegia in patients from Turkey.

Neurol Neurochir Pol 2020 3;54(2):176-184. Epub 2020 Apr 3.

Istanbul University, Istanbul Medical Faculty, Department of Neurology, Istanbul, Turkey.

Objectives: Hereditary spastic paraplegias (HSPs) are a heterogenous group of rare neurodegenerative disorders that present with lower limb spasticity. It is known as complicated HSP if spasticity is accompanied by additional features such as cognitive impairment, cerebellar syndrome, thin corpus callosum, or neuropathy. Most HSP families show autosomal dominant (AD) inheritance. Read More

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