ArticleEuropean journal of human genetics : EJHG2012
Promoter alteration causes transcriptional repression of the POMGNT1 gene in limb-girdle muscular dystrophy type 2O.
Article in European journal of human genetics : EJHG, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Recent insights into limb-girdle muscular dystrophy: Impacts, therapy, and challenges.Histology and histopathology · 2025Review
- Zebrafish as a Model Organism for Research in Rare Genetic Neuromuscular Diseases.International journal of molecular sciences · 2025Review
- Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.Annals of clinical and translational neurology · 2024Article
- Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy.bioRxiv : the preprint server for biology · 2024Article
- High degree of conservation of the enzymes synthesizing the laminin-binding glycoepitope of α-dystroglycan.Open biology · 2021Article
- Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing.Scientific reports · 2017Article
- Evolution of protein N-glycosylation process in Golgi apparatus which shapes diversity of protein N-glycan structures in plants, animals and fungi.Scientific reports · 2017Article
- Malformations of cortical development: genetic mechanisms and diagnostic approach.Korean journal of pediatrics · 2017Review
- Limb-girdle muscular dystrophies - international collaborations for translational research.Nature reviews. Neurology · 2016Review
- Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants.Oncotarget · 2016Article
- Expression pattern in retinal photoreceptors of POMGnT1, a protein involved in muscle-eye-brain disease.Molecular vision · 2016Article
- Mammalian O-mannosylation pathway: glycan structures, enzymes, and protein substrates.Biochemistry · 2014Review
- Genetic basis of limb-girdle muscular dystrophies: the 2014 update.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2014Review
- Identification of mutations in TMEM5 and ISPD as a cause of severe cobblestone lissencephaly.American journal of human genetics · 2012Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Limb-girdle muscular dystrophy type 2O (LGMD2O) belongs to a group of rare muscular dystrophies named dystroglycanopathies, which are characterized molecularly by hypoglycosylation of α-dystroglycan (α-DG). Here, we describe the first dystroglycanopathy patient carrying an alteration in the promoter region of the POMGNT1 gene (protein O-mannose β-1,2-N-acetylglucosaminyltransferase 1), which involves a homozygous 9-bp duplication (-83_-75dup). Analysis of the downstream effects of this mutation revealed a decrease in the expression of POMGNT1 mRNA and protein because of negative regulation of the POMGNT1 promoter by the transcription factor ZNF202 (zinc-finger protein 202). By functional analysis of various luciferase constructs, we localized a proximal POMGNT1 promoter and we found a 75% decrease in luciferase activity in the mutant construct when compared with the wild type. Electrophoretic mobility shift assay (EMSA) revealed binding sites for the Sp1, Ets1 and GATA transcription factors. Surprisingly, the mutation generated an additional ZNF202 binding site and this transcriptional repressor bound strongly to the mutant promoter while failing to recognize the wild-type promoter. Although the genetic causes of dystroglycanopathies are highly variable, they account for only 50% of the cases described. Our results emphasize the importance of extending the mutational screening outside the gene-coding region in dystroglycanopathy patients of unknown aetiology, because mutations in noncoding regions may be the cause of disease. Our findings also underline the requirement to perform functional studies that may assist the interpretation of the pathogenic potential of promoter alterations.
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