Congenital myopathy or myotonia is an inherited muscle related disease presenting at birth or in infancy. The common symptoms of myotonia include lack of muscle tone, delayed motor skills, drooping eyelids, muscle cramp, and so forth. There are seven types of myotonia, including nemaline myopathy, myotubular myopathy, centronuclear myopathy, central core disease, multi-minicore disease, congenital fiber-type disproportion and hyaline body myopathy. In the 1990s, ion channel defects were discovered at the root of several myopathies and defective filament proteins cause the most common myotonia, nemaline myopathy. There have been advances in defining genetic basis of most myotonia subtypes for the past decade. Many myotonias result from mutations in more than one gene; the same gene mutations can lead to different myopathies.
There have been eight genes identified for the most common myotonia, nemaline myopathy, including α-skeletal actin (ACTA1); muscle-specific cofilin (CFL2); nebulin (NEB); slow troponin T (TNNT1); β-tropomyosin (TPM2), slow α-tropomyosin (TPM3), kelch-like family member 40 (KLHL40, also known as KBTBD5) and muscle-specific ubiquitin ligase (KBTBD13). The mutations in NEB are responsible for about 40~50% of nemaline myopathy cases and patients with NEB mutations often have autosomal recessive disease. Since the NEB gene is relatively large, no common mutations or mutations hotspots. In contrast, more than 90% alterations on a smaller gene ACTA1 are dominant missense mutations among ~20~25% of nemaline myopathy cases. Additionally, mutations in KBTBD13 have been identified to cause both nemaline and core-rod myopathy. As for central core disease, the dominant changes in the ryanodine receptor gene (RYR1) are found in most cases. About 60% RYR1 mutations in central core disease locate in the hotspots, uncertain variants are an important problem in RYR1 mutations. Except for genes mentioned above, many others have been identified for the cause of myotonias, including selenoprotein 1 (SEPN1), titin (TTN), dynamin 2 (DNM2), myotubularin (MTM1), Slow/β-cardiac myosin heavy chain (MYH7), etc.
To better understand the relationship between gene variants and different subtypes of myotonia, our platform provides targeted DNA sequencing by the Illumina MiSeq or Ion PGM system. A customizable comprehensive myotonia panel is offered to meet your requirements for research.
| ACTA1 | BIN1 | CACNA1S | CCDC78 | CFL2 |
| CNTN1 | COL12A1 | COL6A1 | COL6A2 | COL6A3 |
| DNM2 | FKBP14 | FLNC | HACD1 | KBTBD13 |
| KHL40 | KLHL40 | KLHL41 | LMOD3 | MEGF10 |
| MTM1 | MYF6 | MYH3 | MYH7 | MYH8 |
| MYL1 | MYO18B | MYPN | NEB | PPA2 |
| PYROXD1 | RYR1 | RYR3 | SCN4A | SELENON |
| SEPN1 | SPEG | STAC3 | TNNT1 | TNNT3 |
| TNNTI2 | TPM2 | TPM3 | TRDN | TTN |
For more information about the Custom Congenital Myopathies/Myotonia Panel or need other amplification requirements, please contact us.
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