molecular diagnosis of limb girdle muscular dystrophies

limb girdle muscular dystrophies (lgmds) are group of neuromuscular disorders which are characterized by progressive muscle weakness and they mostly affect the pelvic and shoulder girdle muscles. this disease can be inherited as autosomal dominant (lgmd1) and autosomal recessive (lgmd2). so far seven autosomal dominant and 20 autosomal recessive forms of this disease have been recognized reflecting high level of genetic heterogeneity. autosomal recessive types constitute about 90% of all cases, and are more likely to happen in countries with high rates of consanguineous marriages such as iran.   the limb-girdle muscular dystrophies typically show degeneration/regeneration (dystrophic changes) on muscle biopsy, which is usually associated with elevated serum creatine kinase concentration. for an affected individual it is necessary to first rule out an x-linked dystrophinopathy such as duchene and becker muscular dystrophies (dmd/bmd). biochemical testings (i.e., protein testing by immunostaining or immunblotting) performed on a muscle biopsy have shown several subtypes such as sarcoglycanopathy, calpainopathy, dysferlinopathy, and o-linked glycosylation defects (also known as dystroglycanopathy). the genetic test is primarily performed to aid prenatal diagnosis and carrier detection. for the one has to rule out x-linked dystrophinopathy such as dmd/bmd. for this one may use mlpa technique. indirect methods such as haplotyping by the use of short tandem repeat (str) markers linked to dystrophin gene have shown to be valuable. mlpa can detect deletion and duplication of dystrophin gene which account for 60 to 70% of dystrophinopathies. if dmd/bmd has been rule out, haplotype analysis using str markers linked to genes responsible for most prevalent forms of lgmds will be performed. the next step is the sanger sequencing of the candidate gene. ruling out of dystrophinopathies especially in pedigrees including only one isolated patient or just male affected patients are diagnostic problems of lgmds which should be concerned. nowadays all these difficulties have been solved by the advent of high-throughput next generation sequencing which soon will replace most cumbersome methods.