Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle 
weakness and the presence of nemaline rods. Five genes have now been associated 
with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin 
(NEB), beta-tropomysin (TPM2) and troponin T (TNNT1). In addition, mutations in 
the ryanodine receptor gene (RYR1) have been associated with core-rod myopathy. 
Here we report linkage in two unrelated families, with a variant of nemaline 
myopathy, with associated core-like lesions. The clinical phenotype consists of 
muscle weakness in addition to a peculiar kind of muscle slowness. A genome-wide 
scan revealed a locus for nemaline myopathy with core-like lesions on chromosome 
15q21-q23 for both families. Combining the two families gave a two-point LOD 
score of 10.65 for D15S993. The alpha-tropomyosin-1 gene (TPM1) located within 
this region is the strongest candidate gene. However, no mutations were found in 
the protein-coding region of TPM1, although small deletions or mutations in an 
intron cannot be excluded. The critical region contains few other candidate 
genes coding for muscle proteins and several genes of unknown function, and has 
not yet been sequenced completely. The novel phenotype of nemaline myopathy in 
the two presented families corresponds to an also novel, as yet uncharacterized, 
genotype.