Abstract
BackgroundLimb-girdle muscular dystrophies are characterized by predominant involvement of the shoulder and pelvic girdle and trunk muscle groups. Currently, there are 31 genes implicated in the different forms of limb-girdle muscular dystrophies, which exhibit similar phenotypes and clinical overlap; therefore, advanced molecular techniques are required to achieve differential diagnosis.MethodsWe investigated 26 patients from Latvia and 34 patients from Lithuania with clinical symptoms of limb-girdle muscular dystrophies, along with 565 healthy unrelated controls from general and ethnic populations using our developed test kit based on the Illumina VeraCode GoldenGate genotyping platform, Ion AmpliSeq Inherited Disease Panel and direct sequencing of mutations in calpain 3 (CAPN3), anoctamin 5 (ANO5) and fukutin related protein (FKRP) genes.ResultsAnalysis revealed a homozygous CAPN3 c.550delA mutation in eight patients and three heterozygous variants in controls: dysferlin (DYSF) c.5028delG, CAPN3 c.2288A > G, and FKRP c.135C > T. Additionally, three mutations within FKRP gene were found: homozygous c.826C > A, and two compound – c.826C > A/c.404_405insT and c.826C > A/c.204_206delCTC mutations, and one mutation within CLCN1 gene – c.2680C > T p.Arg894Ter. ANO5 c.191dupA was not present.ConclusionsGenetic diagnosis was possible in 12 of 60 patients (20 %). The allele frequency of CAPN3 gene mutation c.550delA in Latvia is 0.0016 and in Lithuania - 0.0029. The allele frequencies of CAPN3 gene mutation c.2288A > G and DYSF gene mutation c.4872delG are 0.003.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1058-z) contains supplementary material, which is available to authorized users.
Highlights
Limb-girdle muscular dystrophies are characterized by predominant involvement of the shoulder and pelvic girdle and trunk muscle groups
Common mutations have been identified for some causative genes (for example, calpain 3 (CAPN3) c.550delA or fukutin related protein (FKRP) c.826C > A), Inashkina et al BMC Musculoskeletal Disorders (2016) 17:200 a lot of additional mutations were found in different populations
Patients We investigated 26 patients from Latvia and 34 patients from Lithuania with clinical symptoms of Limb-girdle muscular dystrophies (LGMD)
Summary
Limb-girdle muscular dystrophies are characterized by predominant involvement of the shoulder and pelvic girdle and trunk muscle groups. There are 31 genes implicated in the different forms of limb-girdle muscular dystrophies, which exhibit similar phenotypes and clinical overlap; advanced molecular techniques are required to achieve differential diagnosis. Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of diseases that predominantly affect pelvic and shoulder girdle muscle groups. The advantage of generation sequencing lies in the capability of analyzing whole exomes at a reasonable cost without invasive muscle biopsies. Limitations of this method are related to insufficient exon coverage, leading to a potential lack of a representative examination of all exons [10]
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