ArticleEuropean journal of human genetics : EJHG2013
Expanded spectrum of Pelizaeus-Merzbacher-like disease: literature revision and description of a novel GJC2 mutation in an unusually severe form.
Article in European journal of human genetics : EJHG, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Developmental Delay, Hypomyelination, and Nystagmus: Case and Approach.Neuro-ophthalmology (Aeolus Press) · 2024Article
- Description of Phenotypic Heterogeneity in aMolecular syndromology · 2023Article
- Mechanisms of Diseases Associated with Mutation in GJC2/Connexin 47.Biomolecules · 2023Review
- A novel mutation in GJC2 associated with hypomyelinating leukodystrophy type 2 disorder.Genomics & informatics · 2022Article
- MRI CNS Atrophy Pattern and the Etiologies of Progressive Ataxias.Tomography (Ann Arbor, Mich.) · 2022Review
- The Infantile Leukoencephalopathy-Associated Mutation of C11ORF73/HIKESHI Proteins Generates de novo Interactive Activity with Filamin A, Inhibiting Oligodendroglial Cell Morphological Differentiation.Medicines (Basel, Switzerland) · 2021Article
- Abnormal lymphatic phenotype in a CRISPR mouse model of the human lymphedema-causing Connexin47 R260C point mutation.Lymphology · 2021Article
- Rare Neurologic Disease-Associated Mutations of AIMP1 are Related with Inhibitory Neuronal Differentiation Which is Reversed by Ibuprofen.Medicines (Basel, Switzerland) · 2020Article
- PP1C and PP2A are p70S6K Phosphatases Whose Inhibition Ameliorates HLD12-Associated Inhibition of Oligodendroglial Cell Morphological Differentiation.Biomedicines · 2020Article
- Spinal Cord Involvement in Pediatric-Onset Metabolic Disorders With Mendelian and Mitochondrial Inheritance.Frontiers in pediatrics · 2020Review
- Hypomyelinating leukodystrophy-associated mutation of RARS leads it to the lysosome, inhibiting oligodendroglial morphological differentiation.Biochemistry and biophysics reports · 2019Article
- Compound heterozygous mutations in SNAP29 is associated with Pelizaeus-Merzbacher-like disorder (PMLD).Human genetics · 2019Article
- Novel mutations in the GJC2 gene associated with Pelizaeus-Merzbacher-like disease.Molecular biology reports · 2019Article
- Oculodentodigital Dysplasia: A Hypomyelinating Leukodystrophy with a Characteristic MRI Pattern of Brain Stem Involvement.AJNR. American journal of neuroradiology · 2019Article
- Genetic defects disrupting glial ion and water homeostasis in the brain.Brain pathology (Zurich, Switzerland) · 2018Review
- Neurogenetics of Pelizaeus-Merzbacher disease.Handbook of clinical neurology · 2018Review
- Clinical and Genetic Characteristics of Leukodystrophies in Africa.Journal of neurosciences in rural practice · 2017Review
- GJC2 promoter mutations causing Pelizaeus-Merzbacher-like disease.Molecular genetics and metabolism · 2014Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
Homozygous or compound heterozygous mutations in the GJC2 gene, encoding the gap junction protein connexin47 (Cx47), cause the autosomal recessive hypomyelinating Pelizaeus-Merzbacher-like disease (PMLD1, MIM# 608804). Although clinical and neuroradiological findings resemble those of the classic Pelizaeus-Merzbacher disease, PMLD patients usually show a greater level of cognitive and motor functions. Unpredictably a homozygous missense GJC2 mutation (p.Glu260Lys) was found in a patient presenting with a very severe clinical picture characterised by congenital nystagmus and severe neurological impairment. Also magnetic resonance imaging was unusually severe, showing an abnormal supra- and infratentorial white matter involvement extending to the spinal cord. The novel p.Glu260Lys (c.778G>A) mutation, occurring in a highly conserved motif (SRPTEK) of the Cx47 extracellular loop-2 domain, was predicted, by modelling analysis, to break a 'salt bridge network', crucial for a proper connexin-connexin interaction to form a connexon, thus hampering the correct formation of the connexon pore. The same structural analysis, extended to the previously reported missense mutations, predicted that most changes were expected to have less severe impact on protein functions, correlating with the mild PMLD1 form of the patients. Our study expands the spectrum of PMLD1 and provides evidence that the extremely severe clinical and neuroradiological PMLD1 form of our patient likely correlates with the predicted impairment of gap junction channel assembly resulting from the detrimental effect of the new p.Glu260Lys mutant allele on Cx47 protein.
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