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01.12.2016 | Research article | Ausgabe 1/2016 Open Access

BMC Musculoskeletal Disorders 1/2016

Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies

Zeitschrift:
BMC Musculoskeletal Disorders > Ausgabe 1/2016
Autoren:
Inna Inashkina, Eriks Jankevics, Janis Stavusis, Inta Vasiljeva, Kristine Viksne, Ieva Micule, Jurgis Strautmanis, Maruta S. Naudina, Loreta Cimbalistiene, Vaidutis Kucinskas, Astrida Krumina, Algirdas Utkus, Birute Burnyte, Ausra Matuleviciene, Baiba Lace
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12891-016-1058-z) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

II carried out the molecular genetic studies, participated in the mutation selection and drafted the manuscript. EJ participated in the design of the study and helped to draft the manuscript. JS carried out the molecular genetic studies. IV participated in the mutation selection. KV isolated patients’ DNA. IM, JS, MSN, LC, VK, BB, AM participated in the recruitment of the patients and their diagnosing as neurologists or clinical geneticists. AK participated in the design of the study. AU participated in the design of the study. BL conceived of the study, participated in its design and coordination, participated in the mutation selection, participated in the recruitment of the patients and their diagnosing and helped to draft the manuscript. All authors read and approved the final manuscript.

Authors’ information

Not applicable.

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 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.

Conclusions

Genetic 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.
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