Diagnostics of short tandem repeat expansion variants using massively parallel sequencing and componential tools

Leeuw, Rick H. de; Garnier, Dominique; Kroon, Rosemarie M. J. M.; Horlings, Corinne G.C.; Meijer, Emile de; Buermans, Henk P.J.; Engelen, B.G.M. van; Knijff, Peter de; Raz, Vered

doi:10.1038/s41431-018-0302-4

Cited by 12 publications

(13 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our assays showed high interindividual variations in miRNA expression levels between OPMD patients, and in a few patients, the expression level of specific miRNAs was not different from that found in the control. Among the Dutch OPMD patients symptom severity highly varied and the initial symptom as well [ 50 , 51 ]. It could be expected that few miRNAs would be required as biomarkers for OPMD.…”

Section: Discussionmentioning

confidence: 99%

“…The vastus lateralis muscle biopsy was collected with a Bergstrom needle biopsy and snapped freeze in liquid nitrogen. Collection of saliva and blood from OPMD patients and control subjects was reported in [ 51 ]. Saliva was collected in RNeasy Protect Saliva Mini Kit (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

“… OPMD patients were clinically diagnosed by the neurologist based on the common clinical OPMD symptoms. OPMD was genetically confirmed using a genetic test as described in [ 51 ]. Patients with OPMD-like symptoms without a genetic confirmation were excluded.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy

Raz

Kroon

Mei

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Small non-coding microRNAs (miRNAs) are involved in the regulation of mRNA stability. Their features, including high stability and secretion to biofluids, make them attractive as potential biomarkers for diverse pathologies. This is the first study reporting miRNA as potential biomarkers for oculopharyngeal muscular dystrophy (OPMD), an adult-onset myopathy. We hypothesized that miRNA that is differentially expressed in affected muscles from OPMD patients is secreted to biofluids and those miRNAs could be used as biomarkers for OPMD. We first identified candidate miRNAs from OPMD-affected muscles and from muscles from an OPMD mouse model using RNA sequencing. We then compared the OPMD-deregulated miRNAs to the literature and, subsequently, we selected a few candidates for expression studies in serum and saliva biofluids using qRT-PCR. We identified 126 miRNAs OPMD-deregulated in human muscles, but 36 deregulated miRNAs in mice only (pFDR < 0.05). Only 15 OPMD-deregulated miRNAs overlapped between the in humans and mouse studies. The majority of the OPMD-deregulated miRNAs showed opposite deregulation direction compared with known muscular dystrophies miRNAs (myoMirs), which are associated. In contrast, similar dysregulation direction was found for 13 miRNAs that are common between OPMD and aging muscles. A significant age-association (p < 0.05) was found for 17 OPMD-deregulated miRNAs (13.4%), whereas in controls, only six miRNAs (1.4%) showed a significant age-association, suggesting that miRNA expression in OPMD is highly age-associated. miRNA expression in biofluids revealed that OPMD-associated deregulation in saliva was similar to that in muscles, but not in serum. The same as in muscle, miRNA expression levels in saliva were also found to be associated with age (p < 0.05). Moreover, the majority of OPMD-miRNAs were found to be associated with dysphagia as an initial symptom. We suggest that levels of specific miRNAs in saliva can mark muscle degeneration in general and dysphagia in OPMD.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy

Raz

Kroon

Mei

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…OPMD has been identified throughout the world. Most reported cases are autosomal dominant, but several recessive cases have also been reported (Brais, 2009;de Leeuw et al, 2019). On the protein level, the alanine expansion varies between +1 and +8 over the non-pathogenic 10 alanine track.…”

Section: Oculopharyngeal Muscular Dystrophy (Opmd)mentioning

confidence: 99%

Mouse models for muscular dystrophies: an overview

et al. 2020

Self Cite

View full text Add to dashboard Cite

Muscular dystrophies (MDs) encompass a wide variety of inherited disorders that are characterized by loss of muscle tissue associated with a progressive reduction in muscle function. With a cure lacking for MDs, preclinical developments of therapeutic approaches depend on well-characterized animal models that recapitulate the specific pathology in patients. The mouse is the most widely and extensively used model for MDs, and it has played a key role in our understanding of the molecular mechanisms underlying MD pathogenesis. This has enabled the development of therapeutic strategies. Owing to advancements in genetic engineering, a wide variety of mouse models are available for the majority of MDs. Here, we summarize the characteristics of the most commonly used mouse models for a subset of highly studied MDs, collated into a table. Together with references to key publications describing these models, this brief but detailed overview would be useful for those interested in, or working with, mouse models of MD.

show abstract

“…Sometimes even after extensive investigation with NGS short-read technologies the diagnose remains unknown. This is particularly true in cases with complex expanded alleles 58,59 , where the repeat may be interrupted multiple times. In this case, long read sequencing could be useful.…”

Section: Long Read Sequencing: a Future Not So Distantmentioning

confidence: 99%

Evidence and practices of the use of next generation sequencing in patients with undiagnosed autosomal dominant cerebellar ataxias: a review

Novis

Spitz

Jardim

et al. 2020

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

Autosomal dominant cerebellar ataxias (ADCA) are heterogeneous diseases with a highly variable phenotype and genotype. They can be divided into episodic ataxia and spinocerebellar ataxia (SCA); the latter is considered the prototype of the ADCA. Most of the ADCA are caused by polyglutamine expansions, mainly SCA 1, 2, 3, 6, 7, 17 and Dentatorubral-pallidoluysian atrophy (DRPLA). However, 30% of patients remain undiagnosed after testing for these most common SCA. Recently, several studies have demonstrated that the new generation of sequencing methods are useful for the diagnose of these patients. This review focus on searching evidence on the literature, its usefulness in clinical practice and future perspectives.

show abstract

Diagnostics of short tandem repeat expansion variants using massively parallel sequencing and componential tools

Cited by 12 publications

References 32 publications

Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy

Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy

Mouse models for muscular dystrophies: an overview

Evidence and practices of the use of next generation sequencing in patients with undiagnosed autosomal dominant cerebellar ataxias: a review

Contact Info

Product

Resources

About