Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Inashkina, Inna; Jankevics, Eriks; Stavusis, Janis; Vasiljeva, Inta; Viksne, Kristine; Micule, Ieva; Strautmanis, Jurgis; Naudina, Maruta; Cimbalistiene, Loreta; Kucinskas, Vaidutis; Krumina, Astrida; Utkus, Algirdas; Burnyte, Birute; Matuleviciene, Ausra; Lace, Baiba
• Is Part Of: BMC musculoskeletal disorders. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 6
• Publication Date: 2016-12
• Subjects: Limb-girdle muscular dystrophies -- Illumina VeraCode GoldenGate -- Calpain 3 c.550delA -- Fukutin related protein; Musculoskeletal system -- Diseases -- Periodicals; 616.705
• DOI: 10.1186/s12891-016-1058-z
• Languages: English
• ISSNs: 1471-2474

Abstract

Abstract Background Limb-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. Methods We 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. Results Analysis revealed a homozygousCAPN3 c.550delA mutation in eight patients and three heterozygous variants in controls: dysferlin (DYSF ) c.5028delG, CAPN3 c.2288A > G, andFKRP c.135C > T. Additionally, three mutations withinFKRP 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 withinCLCN1 gene – c.2680C > T p.Arg894Ter.ANO5 c.191dupA was not present. Conclusions Genetic diagnosis was possible in 12 of 60 patients (20 %). The allele frequency ofCAPN3 gene mutation c.550delA in Latvia is 0.0016 and in Lithuania - 0.0029. The allele frequencies ofCAPN3 gene mutation c.2288A > G andDYSF gene mutation c.4872delG are 0.003.