Diagnostic overview of blood‐based dysferlin protein assay for dysferlinopathies. Issue 3 (16th June 2014)

• Record Type: Journal Article
• Authors: Ankala, Arunkanth; Nallamilli, Babi R.; Rufibach, Laura E.; Hwang, Esther; Hegde, Madhuri R.
• Is Part Of: Muscle & nerve. Volume 50:Issue 3(2014:Sep.)
• Page Start: 333
• Page End: 339
• Publication Date: 2014-06-16
• Subjects: Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.24195
• Languages: English
• ISSNs: 0148-639X

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p> <italic>Introduction</italic>: Dysferlin deficiency causes dysferlinopathies. Among peripheral blood mononuclear cells (PBMCs), the dysferlin protein is expressed specifically in CD14⁺ monocytes. <italic>Methods</italic>: We quantified dysferlin protein levels in PBMC lysates of 77 individuals suspected clinically of having a dysferlinopathy to screen for true positives. Subsequent molecular confirmation was done by Sanger sequencing and comparative genomic hybridization arrays to establish diagnosis. <italic>Results</italic>: Of the 44 individuals who had significantly reduced dysferlin levels (≤10%), 41 underwent molecular testing. We identified at least 1 mutation in 85% (35 of 41), and 2 mutations, establishing a dysferlinopathy diagnosis, in 61% (25 of 41) of these individuals. Among those with dysferlin protein levels of &gt;10% (33 of 77), only 1 individual (of 14 who underwent molecular testing) had a detectable mutation. <italic>Conclusions</italic>: Our results suggest that dysferlin protein levels of ≤10% in PBMCs, are highly indicative of primary dysferlinopathies. However, this assay may not distinguish carriers from those with secondary dysferlin reduction. <italic>Muscle Nerve</italic><bold>50</bold>: 333–339, 2014</p> </abstract>