Sirs: We describe a family with adult-onset limb girdle muscular dystrophy 1B (LGMD1B) due to a new mutation in LMNA encoding for lamin A/C. Lamins A/C maintain nuclear shape and provide a structural support for chromosomes [7]. Mutations in LMNA cause a variety of diseases, now called laminopathies: autosomaldominant and autosomal-recessive Emery-Dreifuss muscular dystrophy (AD-EDMD and AR-EDMD) [1], limb girdle muscular dystrophy 1B (LGMD1B) [8], dilated cardiomyopathy (DCM) with conduction defect [3], familial partial lipodystrophy type Dunnigan (FPLP) [11], CharcotMarie-Tooth neuropathy 2B1 (CMT2B1) [10], and several progeria syndromes [2, 9].The molecular mechanisms leading to these different clinical phenotypes are not understood. It appears that different parts of the molecule play different roles in their interaction with other molecules and stability of the protein [4, 7]. The 48 year old female index patient was well until she was 35 years of age when she noticed difficulty in climbing stairs. The muscular weakness was slowly progressive and was accompanied by mild dyspnea. She denied any stiffness or rigidity of her back, elbows or ankles. The family history revealed that the father had died at a young age because of lung cancer but muscle weakness could not be recalled. Her mother was in good health. On physical examination manual muscle testing revealed a moderate limb-girdle weakness with the pelvic girdle being predominantly affected (hip-flexor paresis 3–4/5). There were no contractures (Fig. A and B). The 19 year old daughter had minimal limb girdle weakness without contractures. Cardiac examination was normal. The creatinkinase was 10-times above normal. Metabolically, there were no signs of insulin-resistance, hyperlipidemia or other abnormalities typical of lipodystrophy The muscle specimen showed signs of a mild dystrophy with a normal immunohistochemical analysis. Cardiac examination revealed permanent atrial fibrillation and AV-block III° after cardioversion. A pacemaker was implanted at age 49. Cardiac MRI was performed using a phased array cardiac surface coil. On CINE-MRI images wall motion abnormalities could be detected at the apex and inferoseptal wall of the left ventricle, as well as a delayed contrast enhancement in the same regions (Fig. C). The phenomenon of delayed myocardial enhancement on MRI was first used to detect areas of non-viable myocardium in chronic myocardial infarction [5]. To our knowledge, we are the first to describe this phenomenon in a patient with muscular dystrophy. For mutation analysis of LMNA all exons and the promoter region were amplified [3]. The analysis was confirmed by sequencing in both directions (Fig. D) and subsequently by restriction enzyme analysis (Fig. E). The identified missense mutation exchanges tryptophan at position 498 for cysteine (W498C). The mutation was found in the index patient and in both of her children. Her mother did not carry the mutation. LGMD1B is rare within the LMNA-associated neuromuscular disorders. Whereas only eight mutations have been found leading to LGMD1B the EDMD phenotype is caused by more than 40 mutations spread out over the entire gene [6, 12–14]. On the protein level, tryptophan 498 is located at the C-terminus of betastrand 6 within the globular domain of lamin A/C. At this position there is a conserved aromatic residue in lamins. The side chain of tryptophan 498 is located at the center of a cavity, surrounded by mainly hydrophobic side chains of different beta-strands that are not close in the lamin sequence but in tertiary structure. Interestingly, another mutation associated with the rare LGMD1B phenotype is also found in the globular domain of lamin A/C, Y481H [6]. Y481 is located on beta 5 in a cavity close to W498 (Fig. E). This might be coincidental but could also represent a mutational hotspot in LMNA for LGMD1B.