Severe congenital actin related myopathy with myofibrillar myopathy features

Selcen, Duygu

doi:10.1016/j.nmd.2015.04.002

Cited by 15 publications

(6 citation statements)

References 18 publications

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“…In addition, the genes FHL1 , DNAJB6 , PLEC , LMNA , ACTA1 , HSPB8 , SQSTM and TIA1 were selected as candidate genes because mutations in these genes create overlapping features of MFM that include desmin aggregation, myofibrillar disarray, progressive muscle weakness and atrophy 31 . Mutations in these genes are associated with the diseases scapuloperoneal myopathy, limb‐girdle muscular dystrophy, Emery‐Dreifuss muscular dystrophy, nemaline myopathy, Charcot‐Marie‐Tooth, Welander distal myopathy and MFM‐like inclusion body myopathy 17,31,43–54 …”

Section: Methodsmentioning

confidence: 99%

“…The use of high‐throughput, next‐generation sequencing has increased the number of genetic variants associated with MFM and atypical MFM phenotypes, which are protein aggregate myopathies with more diverse clinical signs than classic MFM 31,42 . These variants are found in four‐and‐half LIM domain 1 ( FHL1 ), 17,43–45 DNAJ/HSP40 homolog subfamily B, member 6 ( DNAJB6 ), 31,46,47 plectin ( PLEC ), 47–49 lamin A/C ( LMNA ), 50,51 alpha‐actin ( ACTA1 ), 31,52 heat‐shock 22‐kd protein 8 ( HSPB8 ) 31,53 and digenic mutations in sequestosome 1 and cytotoxic granule‐associated RNA‐binding protein ( SQSTM1 and TIA1 ) 54 . This brings the total to 16 genes associated with an MFM‐like histological phenotype in humans.…”

Section: Introductionmentioning

confidence: 99%

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Candidate gene expression and coding sequence variants in Warmblood horses with myofibrillar myopathy

Williams

Velez‐Irizarry

Petersen

et al. 2020

Equine Veterinary Journal

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Background Myofibrillar myopathy (MFM) of unknown aetiology has recently been identified in Warmblood (WB) horses. In humans, 16 genes have been implicated in various MFM‐like disorders. Objectives To identify variants in 16 MFM candidate genes and compare allele frequencies of all variants between MFM WB and non‐MFM WB and coding variants with moderate or severe predicted effects in MFM WB with publicly available data of other breeds. To compare differential gene expression and muscle fibre contractile force between MFM and non‐MFM WB. Study design Case‐control. Animals 8 MFM WB, 8 non‐MFM WB, 33 other WB, 32 Thoroughbreds, 80 Quarter Horses and 77 horses of other breeds in public databases. Methods Variants were called within transcripts of 16 candidate genes using gluteal muscle mRNA sequences aligned to EquCab3.0 and allele frequencies compared by Fisher's exact test among MFM WB, non‐MFM WB and public sequences across breeds. Candidate gene differential expression was determined between MFM and non‐MFM WB by fitting a negative binomial generalised log‐linear model per gene (false discovery rate <0.05). The maximal isometric force/cross‐sectional area generated by isolated membrane‐permeabilised muscle fibres was determined. Results None of the 426 variants identified in 16 candidate genes were associated with MFM including 26 missense variants. Breed‐specific differences existed in allele frequencies. Candidate gene differential expression and muscle fibre‐specific force did not differ between MFM WB (143.1 ± 34.7 kPa) and non‐MFM WB (140.2 ± 43.7 kPa) (P = .8). Main limitations RNA‐seq–only assays transcripts expressed in skeletal muscle. Other possible candidate genes were not evaluated. Conclusions Evidence for association of variants with a disease is essential because coding sequence variants are common in the equine genome. Variants identified in MFM candidate genes, including two coding variants offered as commercial MFM equine genetic tests, did not associate with the WB MFM phenotype.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Candidate gene expression and coding sequence variants in Warmblood horses with myofibrillar myopathy

Williams

Velez‐Irizarry

Petersen

et al. 2020

Equine Veterinary Journal

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“…For example nemaline rods can be associated with defects in ACTA1, NEB, CFL2, TPM2, TPM3, TNNT1, RYR1, 3 members of the Kelch family and LMOD3 [6][7][8]. ACTA1 mutations are associated with several structural defects that include nemaline rods (nuclear and/or cytoplasmic), accumulation of actin, cores, caps, fibre type disproportion and also with similarities to a myofibrillar myopathy [9]. The patient we report here adds zebra bodies to the list and illustrates that zebra body myopathy is part of the spectrum of myopathies caused by mutations in ACTA1.…”

Section: Discussionmentioning

confidence: 99%

Zebra body myopathy is caused by a mutation in the skeletal muscle actin gene (ACTA1)

Sewry

Holton

Dick

et al. 2015

Neuromuscular Disorders

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“…Mutations in ACTA1 can cause many types of congenital myopathies. A case with a two-amino-acid duplication in ACTA1 which resembled MFM phenotype has been described (Selcen 2015). The MFM-like features included myofibrillar disorganization of hyaline structures and ectopic or abnormal expression of actin, desmin, α-Bcrystallin, myotilin, dystrophin, and NCAM.…”

Section: Novel Atypical Mfm-like Subtypesmentioning

confidence: 99%

“…Pathogenic mutations in these genes cause mainly clinically typical MFM. Recently, patients with mutations in FHL1, TTN, DNAJB6, PLEC, ACTA1, HSPB8, LMNA, KY, PYROXD1, and SQSTM1, the latter accompanied by a modifying variant in cytotoxic granule-associated RNA-binding protein TIA1, were characterized (Selcen et al 2011;Selcen 2015;Straussberg et al 2016;Winter et al 2016;Ghaoui et al 2016;Sandell et al 2016;O'Grady et al 2016;Niu et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Myofibrillar myopathy in the genomic context

2018

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Myofibrillar myopathy (MFM) is a group of inherited muscular disorders characterized by myofibril dissolution and abnormal accumulation of degradation products. The diagnosis of muscular disorders based on clinical presentation is difficult due to phenotypic heterogeneity and overlapping symptoms. In addition, precise diagnosis does not always explain the disease etiopathology or the highly variable clinical course even among patients diagnosed with the same type of myopathy. The advent of high-throughput next-generation sequencing (NGS) has provided a successful and cost-effective strategy for identification of novel causative genes in myopathies, including MFM. So far, pathogenic mutations associated with MFM phenotype, including atypical MFM-like cases, have been identified in 17 genes: DES, CRYAB, MYOT, ZASP, FLNC, BAG3, FHL1, TTN, DNAJB6, PLEC, LMNA, ACTA1, HSPB8, KY, PYROXD1, and SQSTM + TIA1 (digenic). Most of these genes are also associated with other forms of muscle diseases. In addition, in many MFM patients, numerous genomic variants in muscle-related genes have been identified. The various myopathies and muscular dystrophies seem to form a single disease continuum; therefore, gene identification in one disease impacts the genetic etiology of the others. In this review, we describe the heterogeneity of the MFM genetic background focusing on the role of rare variants, the importance of whole genome sequencing in the identification of novel disease-associated mutations, and the emerging concept of variant load as the basis of the phenotypic heterogeneity.

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Severe congenital actin related myopathy with myofibrillar myopathy features

Cited by 15 publications

References 18 publications

Candidate gene expression and coding sequence variants in Warmblood horses with myofibrillar myopathy

Candidate gene expression and coding sequence variants in Warmblood horses with myofibrillar myopathy

Zebra body myopathy is caused by a mutation in the skeletal muscle actin gene (ACTA1)

Myofibrillar myopathy in the genomic context

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