Exon-Skipping Oligonucleotides Restore Functional Collagen VI by Correcting a Common COL6A1 Mutation in Ullrich CMD
نویسندگان
چکیده
منابع مشابه
Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy.
Mutations in the three collagen VI genes COL6A1, COL6A2 and COL6A3 cause Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). UCMD, a severe disorder characterized by congenital muscle weakness, proximal joint contractures and marked distal joint hyperextensibility, has been considered a recessive condition, and homozygous or compound heterozygous mutations have been defined in CO...
متن کاملUllrich congenital muscular dystrophy and Bethlem myopathy: clinical and genetic heterogeneity.
UNLABELLED Ullrich congenital muscular dystrophy (UCMD), due to mutations in the collagen VI genes, is an autosomal recessive form of CMD, commonly associated with distal joints hyperlaxity and severe course. A mild or moderate involvement can be occasionally observed. OBJECTIVE To evaluate the clinical picture of CMD patients with Ullrich phenotype who presented decreased or absent collagen ...
متن کاملGapmer Antisense Oligonucleotides Suppress the Mutant Allele of COL6A3 and Restore Functional Protein in Ullrich Muscular Dystrophy
Dominant-negative mutations in the genes that encode the three major α chains of collagen type VI, COL6A1, COL6A2, and COL6A3, account for more than 50% of Ullrich congenital muscular dystrophy patients and nearly all Bethlem myopathy patients. Gapmer antisense oligonucleotides (AONs) are usually used for gene silencing by stimulating RNA cleavage through the recruitment of an endogenous endonu...
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Type II collagen mutations have been identified in a phenotypic continuum of chondrodysplasias that range widely in clinical severity. They include achondrogenesis type II, hypochondrogenesis, spondyloepiphyseal dysplasia congenita, spondyloepimetaphyseal dysplasia, Kniest dysplasia, and Stickler syndrome. We report here results that define the underlying genetic defect and consequent altered s...
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Leber congenital amaurosis (LCA) is a severe hereditary retinal dystrophy responsible for congenital or early-onset blindness. The most common disease-causing mutation (>10%) is located deep in intron 26 of the CEP290 gene (c.2991+1655A>G). It creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. In the present study, we show that the use ...
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ژورنال
عنوان ژورنال: Molecular Therapy - Nucleic Acids
سال: 2020
ISSN: 2162-2531
DOI: 10.1016/j.omtn.2020.05.029