In a 50-year-old Italian woman with sporadic dilated cardiomyopathy with conduction defects (CMD1A; 115200), Taylor et al. (2003) identified heterozygosity for a 1718C-T transition in exon 11 of the LMNA gene, resulting in a ser573-to-leu substitution at a highly conserved residue, predicted to affect the carboxyl tail of the lamin A isoform. The mutation was not found in the proband's 2 unaffected offspring or in 300 control chromosomes, but her unaffected 60-year-old sister also carried the mutation.
Van Esch et al. (2006) analyzed the LMNA gene in a 44-year-old male of European descent with arthropathy, tendinous calcifications, and a progeroid appearance (see 248370) and identified homozygosity for the S573L mutation. Progeroid features included a small pinched nose, small lips, micrognathia with crowded teeth, cataract, and alopecia. He also had generalized lipodystrophy, and sclerodermatous skin. The arthropathy affected predominantly the distal femora and proximal tibia in the knee with tendinous calcifications. However, he had normal clavicles and no evidence of acroosteolysis. The authors concluded that he had a novel phenotype. The patient's unaffected 15-year-old son was heterozygous for the mutation, which was not found in 450 control chromosomes. The authors noted that the patient had no evidence of cardiomyopathy and his 70-year-old mother, an obligate heterozygote, had no known cardiac problems.
In a 75-year-old European male with partial lipodystrophy (FPLD2; 151660), Lanktree et al. (2007) identified heterozygosity for the S573L mutation in the LMNA gene.
