Correction to: Splicing mutations in human genetic disorders: examples, detection, and confirmation

Abramowicz, Anna; Gos, Monika

doi:10.1007/s13353-019-00493-z

Cited by 60 publications

(78 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The report by Wehrle et al () described a different mutation (c.1228G > T), at the beginning of exon 9, that also resulted in exclusion of this exon from the mature RNA. It has been previously reported (Abramowicz & Gos, ; Wimmer et al, ) that mutations in different locations can result in exon exclusion. In the categorization of Wimmer et al (), the variant identified by us (variant in the splice donor site causing exon skipping), would be classified as Type I (also possibly as type IV, due to the activation of a cryptic splice site), while the c.1228G > T variant described by Wehrle et al would be classed as a Type V (exonic variant causing exon skipping).…”

Section: Discussionmentioning

confidence: 96%

Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A

Medina

Sandoval

Oliveira

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

The thyroid hormone receptor interactor 11 (TRIP11) gene encodes the Golgi microtubule‐associated protein 210 (GMAP‐210), a protein essential for the operation of the Golgi apparatus. It is known that null mutations in TRIP11 disrupt Golgi function and cause a lethal skeletal dysplasia known as achondrogenesis type 1A (ACG1A), however recently, hypomorphic mutations in that gene have been linked to odontochondrodysplasia (ODCD), a nonlethal skeletal dysplasia characterized by skeletal changes in the spine and in the metaphyseal regions, associated with dentinogenesis imperfecta. Here we present two patients reflecting the phenotypic spectrum related to different TRIP11 variants. The first is a female child with ODCD, for whom a homozygous in‐frame splicing mutation in intron 9 of TRIP11 was identified. The mutation appears to lead to the expression of an alternative TRIP11 transcript, that may explain the less severe radiological alterations in ODCD. The second is a fetus with classical form of ACG1A, associated with typical molecular findings (frameshift) in exon 11 of TRIP11, both novel mutations. The two patients reported here represent the TRIP11 spectrum of skeletal dysplasia ranging from mild to lethal phenotypes, thereby enabling one to suggest a genotype–phenotype correlation in these diseases.

show abstract

Section: Discussionmentioning

confidence: 96%

Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A

Medina

Sandoval

Oliveira

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Depending on the location of the premature stop codon, this results in destruction of the mRNA by nonsense mediated mRNA decay or production of a truncated protein (Lindeboom et al, 2019). mRNA degradation, truncated protein expression, abnormal protein sequences and altered isoform ratios can all disrupt cellular functions and cause disease (Abramowicz and Gos, 2018;Scotti and Swanson, 2016;Sterne-Weiler and Sanford, 2014). Alterations in splicing contribute to diseases ranging from autoimmune diseases (Agrebi et al, 2017) to neurodevelopmental disorders (Xiong et al, 2015) and cancer (Bonnal et al, 2020;Kahles et al, 2018;Rahman et al, 2020;Rhine et al, 2018;Supek et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Mutations primarily alter the inclusion of alternatively spliced exons

Baeza-Centurion

Miñana

Valcárcel

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractGenetic analyses and systematic mutagenesis have revealed that synonymous, non-synonymous and intronic mutations frequently alter the inclusion levels of alternatively spliced exons, consistent with the concept that altered splicing might be a common mechanism by which mutations cause disease. However, most exons expressed in any cell are highly-included in mature mRNAs. Here, by performing deep mutagenesis of highly-included exons and by analysing the association between genome sequence variation and exon inclusion across the transcriptome, we report that mutations only very rarely alter the inclusion of highly-included exons. This is true for both exonic and intronic mutations as well as for perturbations in trans. Therefore, mutations that affect splicing are not evenly distributed across primary transcripts but are focussed in and around alternatively spliced exons with intermediate inclusion levels. These results provide a resource for prioritising synonymous and other variants as disease-causing mutations.

show abstract

“…There are diverse mechanisms by which mutation-induced defects in RNA splicing act as a primary cause of disease [32][33][34].…”

Section: Disease-causing Splicing Mutationsmentioning

confidence: 99%

“…Alternatively, deep intronic mutations disrupt splicing regulatory elements located within introns. Deep intronic mutations can also interfere with the function of transcription regulatory motifs and noncoding RNA genes [33,42].…”

Section: Int J Mol Sci 2019 20 X For Peer Reviewmentioning

confidence: 99%

RNA Splicing Defects in Hypertrophic Cardiomyopathy: Implications for Diagnosis and Therapy

Ribeiro

Furtado

Martins

et al. 2020

IJMS

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is predominantly caused by mutations in genes that encode sarcomere-associated proteins. Effective gene-based diagnosis is critical for the accurate clinical management of patients and their family members. However, the introduction of high-throughput DNA sequencing approaches for clinical diagnostics has vastly expanded the number of variants of uncertain significance, leading to many inconclusive results that limit the clinical utility of genetic testing. More recently, developments in RNA analysis have been improving diagnostic outcomes by identifying new variants that interfere with splicing. This review summarizes recent discoveries of RNA mis-splicing in HCM and provides an overview of research that aims to apply the concept of RNA therapeutics to HCM.

show abstract

Correction to: Splicing mutations in human genetic disorders: examples, detection, and confirmation

Cited by 60 publications

References 0 publications

Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A

Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A

Mutations primarily alter the inclusion of alternatively spliced exons

RNA Splicing Defects in Hypertrophic Cardiomyopathy: Implications for Diagnosis and Therapy

Contact Info

Product

Resources

About