696 results match your criteria Pelizaeus-Merzbacher Disease

Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion.

Development 2022 Oct 24;149(20). Epub 2022 Jun 24.

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Oligodendrocytes, the myelinating cells of the central nervous system, possess great potential for disease modeling and cell transplantation-based therapies for leukodystrophies. However, caveats to oligodendrocyte differentiation protocols ( Ehrlich et al., 2017; Wang et al. Read More

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October 2022

Genotype-phenotype correlation and natural history analyses in a Chinese cohort with pelizaeus-merzbacher disease.

Orphanet J Rare Dis 2022 03 28;17(1):137. Epub 2022 Mar 28.

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

Background: The natural history and genotype-phenotype correlation of Pelizaeus-Merzbacher disease (PMD) of Chinese patients has been rarely reported.

Method: Patients who met the criteria for PMD were enrolled in our study. Genomic analysis was conducted by multiplex ligation probe amplification (MLPA) and Sanger or whole-exome sequencing (WES). Read More

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Activation of the unfolded protein response by Connexin47 mutations associated with Pelizaeus-Merzbacher-like disease.

Mol Cell Neurosci 2022 05 8;120:103716. Epub 2022 Mar 8.

Department of Neurology and Rehabilitation, University of Illinois at Chicago, 912 South Wood Street, Chicago, IL, United States of America; Richard and Loan Hill Department of Biomedical Engineering, University of Illinois at Chicago, 912 South Wood Street, Chicago, IL, United States of America. Electronic address:

Pelizaeus-Merzbacher-like disease type 1 (PMLD1) is a hypomyelinating disorder arising in patients with mutations in GJC2, encoding Connexin47 (Cx47). PMLD1 causes nystagmus, cerebellar ataxia, spasticity and changes in CNS white matter detected by MRI. At least one mutation (p. Read More

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Hypomyelinating Leukodystrophy 8 (HLD8)-Associated Mutation of POLR3B Leads to Defective Oligodendroglial Morphological Differentiation Whose Effect Is Reversed by Ibuprofen.

Neurol Int 2022 Feb 16;14(1):212-244. Epub 2022 Feb 16.

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

POLR3B and POLR3A are the major subunits of RNA polymerase III, which synthesizes non-coding RNAs such as tRNAs and rRNAs. Nucleotide mutations of the RNA polymerase 3 subunit b (polr3b) gene are responsible for hypomyelinating leukodystrophy 8 (HLD8), which is an autosomal recessive oligodendroglial cell disease. Despite the important association between POLR3B mutation and HLD8, it remains unclear how mutated POLR3B proteins cause oligodendroglial cell abnormalities. Read More

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February 2022

Missense mutation of MAL causes a rare leukodystrophy similar to Pelizaeus-Merzbacher disease.

Eur J Hum Genet 2022 Feb 25. Epub 2022 Feb 25.

Division of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.

Leukodystrophies are a heterogenous group of genetic disorders, characterised by abnormal development of cerebral white matter. Pelizaeus-Merzbacher disease is caused by mutations in PLP1, encoding major myelin-resident protein required for myelin sheath assembly. We report a missense variant p. Read More

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February 2022

Hypomyelinating Leukodystrophy 7 (HLD7)-Associated Mutation of POLR3A Is Related to Defective Oligodendroglial Cell Differentiation, Which Is Ameliorated by Ibuprofen.

Neurol Int 2021 Dec 22;14(1):11-33. Epub 2021 Dec 22.

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

Hypomyelinating leukodystrophy 7 (HLD7) is an autosomal recessive oligodendroglial cell-related myelin disease, which is associated with some nucleotide mutations of the RNA polymerase 3 subunit a (polr3a) gene. POLR3A is composed of the catalytic core of RNA polymerase III synthesizing non-coding RNAs, such as rRNA and tRNA. Here, we show that an HLD7-associated nonsense mutation of Arg140-to-Ter (R140X) primarily localizes POLR3A proteins as protein aggregates into lysosomes in mouse oligodendroglial FBD-102b cells, whereas the wild type proteins are not localized in lysosomes. Read More

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December 2021

Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report.

Iran J Med Sci 2021 11;46(6):493-497

Razi Pathobiology and Medical Genetic Laboratory, Karaj, Iran.

Pelizaeus-Merzbacher-Like Disease 1 is a genetic disorder affecting the central nervous system with an autosomal recessive inheritance pattern. It is a rare genetic disorder that affects the central nervous system. In this report, we demonstrated the clinical and paraclinical features of an Iranian consanguine pedigree with suspected hypomyelinating leukodystrophy, without any defined diagnosis. Read More

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November 2021

Emerging Role of the Ketogenic Dietary Therapies beyond Epilepsy in Child Neurology.

Ann Indian Acad Neurol 2021 Jul-Aug;24(4):470-480. Epub 2021 May 11.

Department of Pediatrics (Neurology Division), Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, India.

Ketogenic dietary therapies (KDTs) have been in use for refractory paediatric epilepsy for a century now. Over time, KDTs themselves have undergone various modifications to improve tolerability and clinical feasibility, including the Modified Atkins diet (MAD), medium chain triglyceride (MCT) diet and the low glycaemic index treatment (LGIT). Animal and observational studies indicate numerous benefits of KDTs in paediatric neurological conditions apart from their evident benefits in childhood intractable epilepsy, including neurodevelopmental disorders such as autism spectrum disorder, rarer neurogenetic conditions such as Rett syndrome, Fragile X syndrome and Kabuki syndrome, neurodegenerative conditions such as Pelizaeus-Merzbacher disease, and other conditions such as stroke and migraine. Read More

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Lamin B1 Accumulation's Effects on Autosomal Dominant Leukodystrophy (ADLD): Induction of Reactivity in the Astrocytes.

Cells 2021 09 28;10(10). Epub 2021 Sep 28.

Cellular Signalling Laboratory, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy.

Autosomal dominant leukodystrophy (ADLD) is an extremely rare and fatal neurodegenerative disease due to the overexpression of the nuclear lamina component Lamin B1. Many aspects of the pathology still remain unrevealed. This work highlights the effect of Lamin B1 accumulation on different cellular functions in an ADLD astrocytic in vitro model. Read More

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September 2021

Knockdown of Golgi Stress-Responsive Caspase-2 Ameliorates HLD17-Associated AIMP2 Mutant-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation.

Neurochem Res 2021 Sep 14. Epub 2021 Sep 14.

Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

Hypomyelinating leukodystrophy 17 is an autosomal recessive disease affecting myelin-forming oligodendroglial cells in the central nervous system. The gene responsible for HLD17 encodes aminoacyl-tRNA synthase complex-interacting multifunctional protein 2, whose product proteins form a scaffold that supports aminoacyl-tRNA synthetases throughout the cell body. Here we show that the HLD17-associated nonsense mutation (Tyr35-to-Ter [Y35X]) of AIMP2 localizes AIMP2 proteins as aggregates into the Golgi bodies in mouse oligodendroglial FBD-102b cells. Read More

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September 2021

Prevalence of Human Papillomavirus (HPV) 16 and 18 in Oral Malignant and Potentially Malignant Disorders: A Polymerase Chain Reaction Analysis - A Comparative Study.

Ann Maxillofac Surg 2021 Jan-Jun;11(1):6-11. Epub 2021 Jul 24.

Department of Oral Pathology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India.

Introduction: Human papillomavirus (HPV) are now being increasingly associated as a cause of oral squamous cell carcinomas (OSCC). This study was designed to evaluate the prevalence of HPV in Pelizaeus-Merzbacher disease (PMD) and OSCC using polymerase chain reaction that might help in better understanding of the role played by this virus in the oncogenic process even from its evolution stage.

Materials And Methods: Formalin-fixed paraffin-embedded tissue samples ( = 40) of OSCC and mild, moderate, and severe dysplasia were used for this study. Read More

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Novel Insight into the Potential Pathogenicity of Mitochondrial Dysfunction Resulting from PLP1 Duplication Mutations in Patients with Pelizaeus-Merzbacher Disease.

Neuroscience 2021 11 9;476:60-71. Epub 2021 Sep 9.

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China; Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Peking University First Hospital, Beijing 100083, China. Electronic address:

Among the hypomyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) is a representative disorder. The disease is caused by different types of PLP1 mutations, among which PLP1 duplication accounts for ∼70% of the mutations. Previous studies have shown that PLP1 duplications lead to PLP1 retention in the endoplasmic reticulum (ER); in parallel, recent studies have demonstrated that PLP1 duplication can also lead to mitochondrial dysfunction. Read More

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November 2021

A novel non-human primate model of Pelizaeus-Merzbacher disease.

Neurobiol Dis 2021 10 5;158:105465. Epub 2021 Aug 5.

Divisions of Comparative Medicine Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, United States of America. Electronic address:

Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disorder of the central nervous system (CNS) linked to mutations in the proteolipid protein-1 (PLP1) gene. Although there are multiple animal models of PMD, few of them fully mimic the human disease. Here, we report three spontaneous cases of male neonatal rhesus macaques with the clinical symptoms of hypomyelinating disease, including intention tremors, progressively worsening motor dysfunction, and nystagmus. Read More

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October 2021

Identifying oligodendrocyte enhancers governing Plp1 expression.

Hum Mol Genet 2021 11;30(23):2225-2239

Hunter James Kelly Research Institute, Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.

Oligodendrocytes (OLs) produce myelin in the central nervous system (CNS), which accelerates the propagation of action potentials and supports axonal integrity. As a major component of CNS myelin, proteolipid protein 1 (Plp1) is indispensable for the axon-supportive function of myelin. Notably, this function requires the continuous high-level expression of Plp1 in OLs. Read More

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November 2021

Pathology of the neurovascular unit in leukodystrophies.

Acta Neuropathol Commun 2021 06 3;9(1):103. Epub 2021 Jun 3.

Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam and Amsterdam Neuroscience, de Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.

The blood-brain barrier is a dynamic endothelial cell barrier in the brain microvasculature that separates the blood from the brain parenchyma. Specialized brain endothelial cells, astrocytes, neurons, microglia and pericytes together compose the neurovascular unit and interact to maintain blood-brain barrier function. A disturbed brain barrier function is reported in most common neurological disorders and may play a role in disease pathogenesis. Read More

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Regulation of ClC-2 Chloride Channel Proteostasis by Molecular Chaperones: Correction of Leukodystrophy-Associated Defect.

Int J Mol Sci 2021 May 30;22(11). Epub 2021 May 30.

Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.

The ClC-2 channel plays a critical role in maintaining ion homeostasis in the brain and the testis. Loss-of-function mutations in the ClC-2-encoding human gene are linked to the white matter disease leukodystrophy. -deficient mice display neuronal myelin vacuolation and testicular degeneration. Read More

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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 04 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 08 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 Oct 30;66(10):1035-1037. 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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October 2021

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

Stem Cell Reports 2021 04 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 02 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 Oct 28;64(10):1645-1660. 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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October 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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