A gene for autosomal recessive nemaline myopathy assigned to chromosome 2q by linkage analysis.

Clinical genetic evidence suggests the existence of an autosomal recessive form of congenital nemaline myopathy in addition to the autosomal dominant one(s). One mutation in an Australian kindred has been identified as causing an autosomal dominant form of the disease. This mutation in the alpha-tropomyosin gene TPM3 has previously been excluded as causing autosomal recessive nemaline myopathy. We searched systematically for genetic linkage to autosomal recessive nemaline myopathy (NEM2) by studying microsatellite marker alleles in seven multiplex families from Finland, Denmark, Wales, England and The Netherlands. Significant evidence of linkage was found to markers of chromosome 2q, the highest multipoint lod score value being 5.34 for the marker D2S151. Recombinant genotypes in affected individuals demarcate the the region in which the NEM2 gene is likely to reside as a 13 cM region between the markers D2S150 and D2S142. These results confirm the existence of at least one distinctive form of autosomal recessive nemaline myopathy and provide a basis for the identification of its gene.