title: Novel diagnostic features of dysferlinopathies.
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.
authors.affiliation: Department of Pediatrics, Neuromuscular Division, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Xiomara Q
authors.initials: XQ
authors.lastname: Rosales
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.forename: Sarah
authors.initials: S
authors.lastname: Lewis
authors.forename: Malik
authors.initials: M
authors.lastname: Vinod
authors.forename: Devon L
authors.initials: DL
authors.lastname: Thrush
authors.forename: Caroline
authors.initials: C
authors.lastname: Astbury
authors.forename: Robert
authors.initials: R
authors.lastname: Pyatt
authors.forename: Shalini
authors.initials: S
authors.lastname: Reshmi
authors.forename: Zarife
authors.initials: Z
authors.lastname: Sahenk
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
mesh_terms: D000293:Adolescent; D000328:Adult; D000682:Amyloid / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D000073939:Dysferlin; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007150:Immunohistochemistry; D007866:Leg / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009000:Monocytes / Q000737:chemistry; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D055815:Young Adult
chemical_list: D000682:Amyloid; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D004247:DNA