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ANO 5 ‐ m uscular dystrophy: clinical, pathological and molecular findings
Author(s) -
Liewluck T.,
Winder T. L.,
Dimberg E. L.,
Crum B. A.,
Heppelmann C. J.,
Wang Y.,
Bergen H. R.,
Milone M.
Publication year - 2013
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12191
Subject(s) - medicine , pathological , neuroscience , biology
Background and purpose Anoctamin 5 ( ANO 5) is a putative intracellular calcium‐activated chloride channel. Recessive mutations in ANO 5 cause primary skeletal muscle disorders (limb‐girdle muscular dystrophy 2L and distal muscular dystrophy), which are phenotypically similar to dysferlinopathy, a muscular dystrophy due to dysferlin‐encoding gene ( DYSF ) mutations. Methods This study reports the phenotype and genotype of seven unrelated patients with ANO 5 ‐muscular dystrophy. Results Three patients had amyloid deposition in muscle and two had cardiac involvement. An additional patient without skeletal muscle amyloidosis had cardiac involvement with septal hypokinesis and supraventricular tachycardia requiring ablation. Amyloid subtyping using laser capture microdissection and mass spectrometry‐based proteomic analysis did not identify ANO 5 or any fragment of ANO 5 in the amyloid deposits, but detected other known amyloidogenic proteins. Three patients had myotonic discharges without clinical myotonia. Four ANO 5 mutations are novel, including a heterozygous 0.4 Mb deletion involving the entire ANO 5 gene. Conclusions The results of the present study suggest that ANO 5 mutations can be associated with amyloid deposition in muscle, but the nature of the amyloid deposits remains indeterminate, as does their relationship with cardiac involvement. ANO 5 analysis should be considered in cases of muscle amyloid deposition of indeterminate etiology. Electrical myotonia can accompany ANO 5‐muscular dystrophy.