Genotype-phenotype analysis in X-linked Emery-Dreifuss muscular dystrophy and identification of a missense mutation associated with a milder phenotype

Direct sequencing of the emerin gene in 22 families with Emery-Dreifuss mus cular dystrophy (EMD) revealed mutations in 21 (95%), confirming that emeri n mutations can be identified in the majority of families with X-linked EMD . Most emerin mutations result in absence of the protein. In this study thr ee mutations (a missense mutation Pro183Thr and two in-frame deletions remo ving residues 95-99 and 236-241, respectively) were unusual in being associ ated with expression of mutant protein. The phenotype in these families was compared in detail with the clinical features in cases with typical null m utations. For the in-frame deletions there were no significant differences. In the family with the missense mutation the phenotype was milder. Age at onset was later for first symptoms and for development of ankle contracture s and muscle weakness. These findings have diagnostic implications as well as pointing to functionally important regions of the emerin protein. (C) 19 99 Elsevier Science B.V. All rights reserved.