Unusual expression of emerin in a patient with X-linked Emery±Dreifuss muscular dystrophy C. Di Blasi a , L. Morandi a , M. Raffaele di Barletta b , S. Bione b , P. Bernasconi a , M. Cerletti a , R. Bono c , F. Blasevich a , D. Toniolo b , M. Mora a, * a Department of Neuromuscular Diseases, Istituto Nazionale Neurologico `C. Besta', Via Celoria 11, 20133 Milan, Italy b Institute of Genetics, Biochemistry and Evolution, CNR, Pavia, Italy c Department of Pediatric Neurology, Istituto Nazionale Neurologico `C. Besta', Milan, Italy Received 2 July 1999; received in revised form 22 March 2000; accepted 23 March 2000 Abstract We report on a patient with the typical clinical ®ndings of Emery±Dreifuss muscular dystrophy due to a mutation in the emerin gene that should have produced a higher molecular weight protein. Immunohistochemical analysis showed emerin localized only in the cytoplasm of muscle ®bres and lymphoblastoid cells. The emerin molecule contained the nucleoplasmic domain and the transmembrane domain respon- sible for nuclear membrane targeting, so its incorrect localization and lack of function could be due to abnormal folding resulting in rapid degradation or inability to bind other nuclear proteins. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Emerin; Emery±Dreifuss muscular dystrophy; Nuclear membrane protein; Immunohistochemistry 1. Introduction Emery±Dreifuss syndrome is a genetically heterogeneous entity characterized by early contractures, slowly progres- sive muscle wasting and weakness and cardiomyopathy, usually presenting as heart-block with risk of sudden death [1]. Mutations in at least two genes cause Emery± Dreifuss muscular dystrophy (EDMD); the STA gene [2] encoding emerin, is responsible for the X-linked form, and the LMNA gene encoding lamin A/C is responsible for the autosomal dominant form [3]. Emerin, a small protein of 254 amino acids, localizes to the inner nuclear membrane of numerous cell types. Amino acid sequence homology [2], cellular localization [4±6] and biochemical and molecular characteristics [7] suggest that emerin is a member of the nuclear lamin-associated protein family. Several mutations have been identi®ed in the STA gene, most are nonsense and cause complete loss of emerin [8]. A few missense mutations produce a protein of reduced mole- cular weight and expression [2,6]. We report here on a patient with X-linked EDMD and unusual emerin expres- sion caused by a mutation in the STA gene. 2. Materials and methods 2.1. Case report The patient is a 14-year-old boy who was ®rst seen at our institute at age 6 years for mild weakness, some dif®culty in running and frequent sudden falls while walking. On neuro- logical examination he presented hypotrophic and hypo- tonic limb muscles, mild weakness of abdominal and distal leg muscles causing dif®culty in walking on heel and rising from the ¯oor. His intelligence quotient (IQ), assessed by the Wechsler preschool scale and the primary scale of intelligence (WPPSI), was moderately reduced (68). CK was about 2.5 normal value, ECG was normal, EMG showed neurogenic potentials suggesting involvement of the second motor neuron. A muscle biopsy showed increased endomysial connective tissue, ®bre size variabil- ity, hypertrophic and hypotrophic angulated ®bres, central nuclei and splittings. Numerous large cores were observed on NADH staining; ATPase showed type I grouping; type I ®bres were hypotrophic. Disease progression was very slow. Elbow and Achilles tendon retractions (158), ®rst observed at 9 years, progressively worsened so that the patient under- went operations to lengthen the Achilles tendons at age 11 years and to lengthen elbow ¯exors at 13 years. When the patient was last seen at 14 years neck and trunk ¯exors, Neuromuscular Disorders 10 (2000) 567±571 0960-8966/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S0960-8966(00)00145-0 www.elsevier.com/locate/nmd * Corresponding author. Tel.: 139-2-2394413; fax: 139-2-70633874.