Two distal mutations in the gene encoding emerin have profoundly differenteffects on emerin protein expression

Emerin. the product of the gene responsible for X-linked Emery-Dreifuss mus cular dystrophy (EDMD), has a ubiquitous tissue distribution and is localis ed to the nuclear envelope. We present here the relationship between emerin protein expression, nuclear localization and clinical phenotype for two di stal mutations identified in unrelated EDMD patients. The first mutation pr edicts the replacement of the last eight amino acids of emerin with the add ition of 101 amino acids, but no emerin expression is detected. The second mutation, 35 bp upstream from the first mutation, deletes six amino acids f rom the transmembrane region, bur in this case emerin expression is seen. E merin from this second patient is expressed at reduced levels, mistargeted and has altered biochemical properties compared to wild type emerin. In bot h cases the clinical phenotype was similar to patients with typical null mu tations. 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 t ail prevents nuclear localization. (C) 2000 Elsevier Science B.V. AU rights reserved.