A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy

Scacheri, Peter C.; Hoffman, Eric P.; Fratkin, Jonathan D.; Semino–Mora, Cristina; Senchak, Andrew J.; Davis, Mark; Laing, Nigel G.; Vedanarayanan, Vetta; Subramony, S. H.

doi:10.1212/wnl.55.11.1689

Cited by 136 publications

(83 citation statements)

References 30 publications

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“…Histopathological features: Typical RYR1-related CCD is characterised by well-defined, single or multiple, central or eccentric cores running a significant extent along the longitudinal muscle fibre axis on muscle biopsy. 14 In cases with suggestive clinical features but less specific histopathological findings such as type 1 predominance, uniformity, 15 or cores and rods, 16,17 muscle MRI may be more indicative of RYR1 involvement than muscle biopsy (see below). Muscle MR imaging: Muscle MR imaging in RYR1-related CCD shows a characteristic and consistent pattern of selective involvement, which may aid genetic testing and distinguish from core myopathies with different genetic backgrounds.…”

Section: Analytical Methods Selection Criteriamentioning

confidence: 99%

“…Combination of central cores and nemaline rods in particular may also be seen with certain RYR1 mutations. 16,17 2.4 Clinical specificity (proportion of negative tests if the disease is not present) No precise data regarding the clinical specificity of RYR1 testing in CCD are currently available, however, clinical specificity is likely to be o100% considering the large number of sequence variations of uncertain significance identified in the RYR1 gene. In most cases, a detailed clinical assessment and muscle biopsy will have been performed before genetic testing; therefore, presence of the condition is a prerequisite for the initiation of genetic testing but also of importance for the interpretation of RYR1 variations of uncertain significance.…”

Section: Clinical Sensitivity (Proportion Of Positive Tests If the DImentioning

confidence: 99%

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Clinical utility gene card for: Central core disease

et al. 2011

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Section: Analytical Methods Selection Criteriamentioning

confidence: 99%

Section: Clinical Sensitivity (Proportion Of Positive Tests If the DImentioning

confidence: 99%

Clinical utility gene card for: Central core disease

et al. 2011

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“…The two CCD-associated aSKA mutants induce cores, which differ in size, number and appearance [Kaindl et al, 2004]. Muscle cells from CCD-patients can also display rods, in addition to cores, thereby combining hallmarks for both NM and core myopathies [Scacheri et al, 2000;Gommans et al, 2003;Agrawal et al, 2007] and suggesting there is a link or a common molecular mechanism between both diseases [Vandamme et al, 2009].…”

Section: Mutations In Aska Cause Various Congenital Myopathiesmentioning

confidence: 99%

Actin isoform expression patterns during mammalian development and in pathology: Insights from mouse models

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Vandamme

Vandekerckhove

et al. 2009

Cell Motil. Cytoskeleton

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The dynamic actin cytoskeleton, consisting of six actin isoforms in mammals and a variety of actin binding proteins is essential for all developmental processes and for the viability of the adult organism. Actin isoform specific functions have been proposed for muscle contraction, cell migration, endo-and exocytosis and maintaining cell shape. However, these specific functions for each of the actin isoforms during development are not well understood. Based on transgenic mouse models, we will discuss the expression patterns of the six conventional actin isoforms in mammals during development and adult life. Ablation of actin genes usually leads to lethality and affects expression of other actin isoforms at the cell or tissue level. A good knowledge of their expression and functions will contribute to fully understand severe phenotypes or diseases caused by mutations in actin isoforms. Cell Motil. Cytoskeleton 66: 798-815, 2009. '

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“…To exclude from the search for a seventh NM gene in those Turkish families that might have a mutation in a known NM gene, we analysed the families for linkage to the known NM gene loci, and also to the mixed core-rod myopathy ryanodine receptor (RYR1) (OMIM 180901) locus on chromosome 19, 10,11 and to the core-rod locus on chromosome 15. 12 In the chromosomal region 1q12-21.2 where TPM3 is located, we analysed eight microsatellite markers encompassing a region of 18 cM; D1S252, D1S498, D1S2347, D1S2858, D1S305, D1S2624, D1S2635, and D1S484.…”

Section: Linkage Studiesmentioning

confidence: 99%

Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin

et al. 2008

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To date, six genes are known to cause nemaline (rod) myopathy (NM), a rare congenital neuromuscular disorder. In an attempt to find a seventh gene, we performed linkage and subsequent sequence analyses in 12 Turkish families with recessive NM. We found homozygosity in two of the families at 1q12-21.2, a region encompassing the c-tropomyosin gene (TPM3) encoding slow skeletal muscle a-tropomyosin, a known NM gene. Sequencing revealed homozygous deletion of the first nucleotide of the last exon, c.913delA of TPM3 in both families. The mutation removes the last nucleotide before the stop codon, causing a frameshift and readthrough across the termination signal. The encoded aTm slow protein is predicted to be 73 amino acids longer than normal, and the extension to the protein is hypothesised to be unable to form a coiled coil. The resulting tropomyosin protein may therefore be non-functional. The affected children in both families were homozygous for the mutation, while the healthy parents were mutation carriers. Both of the patients in Family 1 had the severe form of NM, and also an unusual chest deformity. The affected children in Family 2 had the intermediate form of NM. Muscle biopsies showed type 1 (slow) fibres to be markedly smaller than type 2 (fast) fibres. Previously, there had been five reports, only, of NM caused by mutations in TPM3. The mutation reported here is the first deletion to be identified in TPM3, and it is likely to be a founder mutation in the Turkish population.

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A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy

Cited by 136 publications

References 30 publications

Clinical utility gene card for: Central core disease

Clinical utility gene card for: Central core disease

Actin isoform expression patterns during mammalian development and in pathology: Insights from mouse models

Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin

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