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Novel diagnostic features of dysferlinopathies
Author(s) -
Rosales Xiomara Q.,
GastierFoster Julie M.,
Lewis Sarah,
Vinod Malik,
Thrush Devon L.,
Astbury Caroline,
Pyatt Robert,
Reshmi Shalini,
Sahenk Zarife,
Mendell Jerry R.
Publication year - 2010
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21650
Subject(s) - dysferlin , phenotype , limb girdle muscular dystrophy , muscular dystrophy , colocalization , pathology , biology , mutation , medicine , genetics , gene , microbiology and biotechnology
Abstract Reports of dysferlinopathy have suggested a clinically heterogeneous group of patients. We identified specific novel molecular and phenotypic features that help distinguish dysferlinopathies from other forms of limb‐girdle muscular dystrophy (LGMD). A detailed history, physical exam, and protein and mutation analysis of genomic DNA was done for all subjects. Five of 21 confirmed DYSF gene mutations were not previously reported. A distinct “bulge” of the deltoid muscle in combination with other findings was a striking feature in all patients. Six subjects had atypical calf enlargement, and 3 of these exhibited a paradoxical pattern of dysferlin expression: severely reduced by direct immunofluorescence with overexpression on Western blots. Six patients showed amyloid deposits in muscle that extended these findings to new domains of the dysferlin gene, including the C2G domain. Correlative studies showed colocalization of amyloid with deposition of dysferlin. The present data further serve to guide clinicians facing the expensive task of molecular characterization of patients with an LGMD phenotype. Muscle Nerve 42: 14–21, 2010