Limb-girdle muscular dystrophy (LGMD) is a set of disorders that cause weakness in the shoulder girdle and pelvic girdle. LGMD is progressive and can be categorized into different subtypes by gene and inheritance. At least 20 different types of LGMD have been identified, and most forms of LGMD are inherited in an autosomal recessive manner; whereas several rare forms are inherited in an autosomal dominant pattern. Autosomal dominant LGMD, or LGMD1 has been recognized nine subtypes (LGMD1A-I) which occur less frequently comparatively. LGMD1 progresses at a slower rate and has variable symptoms. Each gene mutation can cause several different groups of symptoms. About 90% of LGMD are autosomal recessive LGMD, or LGMD2, and there are 26 subtypes (LGMDA-Z), characterized by progressive weakness of muscles of legs, arms, shoulders and pelvic girdle. As a genetic disorder, genetic alterations have been determined by the combination of genes for particular trait.
There have been discovered 35 genes associated to different subtypes so for. Less than 10% of all LGMD cases are diagnosed as LGMD1 and are related to particular cases of mutations in genes that may be also involved in other disorders, such as caveolin 3, myotilin, or lamin A/C. Lamin A/C (LMNA) gene locates on chr.1q22, and gives rise to at least three isoforms (lamin A, C, lamin A△10). Two main isoform lamin A and C are component of the fibrous nuclear lamina and play different roles in cell activities, including mechanical nuclear membrane maintenance and gene regulation. The LGMD1B is related to heterozygous truncating mutations of LMNA, which lead to a loss of function. On the other hand, the missense mutations of LMNA gene in Emery-Dreifuss muscular dystrophy (EDMD) cause dominant-negative or toxic gain-of-function progress. The most frequent LGMD worldwide is LGMD2A, which is caused by Calpain 3 (CAPN3) gene mutations. CAPN3 encodes a muscle-specific member of the calpain large subunit family that binds to titin. Calpains are intracellular nonlysosomal cysteine proteases and can modify target proteins' properties by cleaving them. What's more, there have been more than 300 mutations in CAPN3 identified in LGMD2A cases. Similar to LMNA and CAPN3 in LGMD1B and LGMD2A, respectively, at least one gene mutation has been shown related to each subtype of LGMD, such as DNAJB6 mutations in LGMD1D, DES mutations in LGMD1E, and so forth.
To have better acknowledgement of relationship between gene mutations and different types LGMD, our platform provides targeted DNA sequencing by the Illumina MiSeq or Ion PGM system, and a comprehensive LGMD panel library. Panel genes can be customized as your research requires for genetic testing of LGMD.
For more information about the Custom Limb Girdle Muscular Dystrophy Panel or need other amplification requirements, please contact us.