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DNA sequencing errors in molecular diagnostics of filamin myopathy
-
Zagaa Odgerel
Published/Copyright:
June 28, 2010
Abstract
Background: Filamin myopathy is a neuromuscular disorder manifesting with predominantly limb-girdle muscle weakness and in many patients with diaphragm paralysis and cardiomyopathy, caused by mutations in the filamin C (FLNC) gene. Molecular diagnosis of filamin myopathy based on direct DNA sequencing of coding exons is compromised by the presence of a high homology pseudogene (pseFLNC) located approximately 53.6 kb downstream of the functional FLNC gene on chromosome 7q.
Methods: Molecular cloning, RT-PCR and real-time PCR methods were used to detect sequence differences between the FLNC and pseFLNC that are implicated in known or potential molecular diagnostic errors. Overall, 50 patients with a phenotype resembling filamin myopathy have been screened for mutations in FLNC.
Results:FLNC sequence inconsistencies caused by the interference from pseFLNC were identified and diagnostic errors involving, in particular, the detection of the most frequent disease-causing FLNC p.W2710X mutation resolved. Mismatches between the FLNC and pseFLNC sequences were tabulated for future use.
Conclusions: We devise a strategy that allows one to discern mutations occurring in the functional FLNC from those harbored in pseFLNC, thus preventing possible complications in future research and patient genetic testing.
Clin Chem Lab Med 2010;48:1409–14.
Keywords: filamin C (FLNC) gene; filaminopathy; mutation-screening; myofibrillar myopathy; pseudogene
Received: 2010-2-23
Accepted: 2010-4-22
Published Online: 2010-06-28
Published in Print: 2010-10-01
©2010 by Walter de Gruyter Berlin New York
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Keywords for this article
filamin C (FLNC) gene;
filaminopathy;
mutation-screening;
myofibrillar myopathy;
pseudogene
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