Novel Mutation in the MECP2 Gene Identified in a Group of Rett Syndrome Patients from Ukraine

Chernushyn, S. Yu.; Gulkovskyi, R. V.; Livshits, Liudmyla

doi:10.3103/s0095452718040023

Cited by 2 publications

(2 citation statements)

References 16 publications

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“…Nonsense mutations are found in about 11% of genetic disorders such as cystic fibrosis (CF) [ 17 ], Duchenne muscular dystrophy (DMD) [ 18 ], spinal muscular atrophy [ 19 , 20 ], neurofibromatosis [ 21 ], retinitis pigmentosa [ 22 , 23 , 24 ], lysosomal storage disease [ 13 , 25 , 26 ], Rett syndrome [ 27 ], Shwachman–Diamond syndrome [ 28 , 29 ], and Usher’s syndrome (USH) [ 30 ]. In this context and despite its limits, the translational readthrough of PTCs can represent a valuable pharmaceutical approach to target the specific genetic defect caused by nonsense mutations.…”

Section: Introductionmentioning

confidence: 99%

Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems

Pibiri

Melfi

Tutone

et al. 2020

IJMS

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Cystic fibrosis (CF) patients develop a severe form of the disease when the cystic fibrosis transmembrane conductance regulator (CFTR) gene is affected by nonsense mutations. Nonsense mutations are responsible for the presence of a premature termination codon (PTC) in the mRNA, creating a lack of functional protein. In this context, translational readthrough-inducing drugs (TRIDs) represent a promising approach to correct the basic defect caused by PTCs. By using computational optimization and biological screening, we identified three new small molecules showing high readthrough activity. The activity of these compounds has been verified by evaluating CFTR expression and functionality after treatment with the selected molecules in cells expressing nonsense–CFTR–mRNA. Additionally, the channel functionality was measured by the halide sensitive yellow fluorescent protein (YFP) quenching assay. All three of the new TRIDs displayed high readthrough activity and low toxicity and can be considered for further evaluation as a therapeutic approach toward the second major cause of CF.

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Section: Introductionmentioning

confidence: 99%

Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems

Pibiri

Melfi

Tutone

et al. 2020

IJMS

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“…Unfortunately, nonsense mutations are the cause of about 11% of all genetic disorders in humans [8,9]. In particular, it was observed that stop mutations are associated to disorders such as cystic fibrosis (CF) [6], Duchenne muscular dystrophy (DMD) [10], spinal muscular atrophy [11,12], neurofibromatosis [13], retinitis pigmentosa [14,15], lysosomal storage disease [16], ataxia telangiectasia (AT) [17], Hurler’s syndrome (HS) [6], Rett syndrome [18], Shwachman–Diamond syndrome [19], Usher’s syndrome (USH) [20], Hemophilia A and B [21], Tay–Sachs disease [22], and several forms of cancer [23].…”

Section: Introductionmentioning

confidence: 99%

Strategies against Nonsense: Oxadiazoles as Translational Readthrough-Inducing Drugs (TRIDs)

Campofelice

Lentini

Leonardo

et al. 2019

IJMS

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This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison to aminoglycosides. Additionally, recent results on the efficiency of new candidate TRIDs in restoring the production of the cystic fibrosis transmembrane regulator (CFTR) protein will be presented. Finally, a prospectus on complementary strategies to enhance the effect of TRIDs will be illustrated together with a conclusive paragraph about perspectives, opportunities, and caveats in developing small molecules as TRIDs.

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Novel Mutation in the MECP2 Gene Identified in a Group of Rett Syndrome Patients from Ukraine

Cited by 2 publications

References 16 publications

Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems

Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems

Strategies against Nonsense: Oxadiazoles as Translational Readthrough-Inducing Drugs (TRIDs)

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