title: Two distal mutations in the gene encoding emerin have profoundly different effects on emerin protein expression.
abstract: Emerin, the product of the gene responsible for X-linked Emery-Dreifuss muscular dystrophy (EDMD), has a ubiquitous tissue distribution and is localised to the nuclear envelope. We present here the relationship between emerin protein expression, nuclear localization and clinical phenotype for two distal mutations identified in unrelated EDMD patients. The first mutation predicts the replacement of the last eight amino acids of emerin with the addition of 101 amino acids, but no emerin expression is detected. The second mutation, 35 bp upstream from the first mutation, deletes six amino acids from the transmembrane region, but in this case emerin expression is seen. Emerin from this second patient is expressed at reduced levels, mistargeted and has altered biochemical properties compared to wild type emerin. In both cases the clinical phenotype was similar to patients with typical null mutations. We discuss these data in comparison with previous reports of other C-terminal mutations in the emerin gene and suggest that the efficiency of emerin's nuclear membrane localization is affected by the hydrophobicity (and possibly length) of its transmembrane region, and a longer C-terminal tail prevents nuclear localization.
authors.affiliation: Department of Medical Genetics, Cambridge Institute of Medical Research, Addenbrooke's Hospital, UK. jae11@mole.bio.cam.ac.uk
authors.forename: J A
authors.initials: JA
authors.lastname: Ellis
authors.forename: C A
authors.initials: CA
authors.lastname: Brown
authors.forename: L D
authors.initials: LD
authors.lastname: Tilley
authors.forename: J
authors.initials: J
authors.lastname: Kendrick-Jones
authors.forename: J E
authors.initials: JE
authors.lastname: Spence
authors.forename: J R
authors.initials: JR
authors.lastname: Yates
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D017353:Gene Deletion; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D009687:Nuclear Proteins; D010641:Phenotype; D010766:Phosphorylation; D013347:Subcellular Fractions / Q000378:metabolism; D013946:Thymopoietins / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin