title: Centronuclear myopathy with cataracts due to a novel dynamin 2 (DNM2) mutation.
abstract: Dynamin 2 (DNM2)-related dominant centronuclear myopathy is usually a mild disorder, but more severe variants have been associated with mutations affecting the pleckstrin homology (PH) domain of the protein, mainly implicated in different forms of Charcot-Marie-Tooth Disease (CMT). Whilst DNM2-related CMT may feature non-neurological findings including cataracts, this has not been reported in DNM2-related centronuclear myopathy. We report a girl presenting from birth with hypotonia, respiratory and feeding difficulties. Motor development was delayed and at 9years she lost the ability to walk. She had ptosis, external ophthalmoplegia and bilateral cataracts. Muscle biopsy showed increase in central nuclei with type 1 hypotrophy and fibrosis. DNM2 screening revealed a novel heterozygous substitution (c.1862T>C; p.Leu621Pro) affecting the PH domain of the protein. Her further course was progressive and at 14years she died from respiratory failure. Our findings expand the phenotypical spectrum associated with DNM2 mutations and provide a new clinical indicator for involvement of this gene in patients with centronuclear myopathy.
authors.affiliation: Clinical Neuroscience Division, King's College, London, UK. Heinz.Jungbluth@gstt.nhs.uk
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
authors.forename: Tom
authors.initials: T
authors.lastname: Cullup
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lillis
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhou
authors.forename: Stephen
authors.initials: S
authors.lastname: Abbs
authors.forename: Caroline
authors.initials: C
authors.lastname: Sewry
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D002386:Cataract / Q000235:genetics*; D002648:Child; D018450:Disease Progression; D034285:Dynamin II / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018482:Muscle, Skeletal / Q000473:pathology; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D034285:Dynamin II