In a family (family C) diagnosed with limb-girdle muscular dystrophy type 1B (LGMD1B), which was reclassified as Emery-Dreifuss muscular dystrophy-2 (EDMD2; 181350) by Straub et al. (2018), Muchir et al. (2000) found a G-to-A transition in exon 6 of the LMNA gene, resulting in a substitution of histidine for arginine-377 (R377H). This family was previously reported by van der Kooi et al. (1996, 1997).
Taylor et al. (2003) identified heterozygosity for the R377H mutation in an American family of British descent with autosomal dominant dilated cardiomyopathy and mild limb-girdle muscular disease.
Charniot et al. (2003) described a French family with autosomal dominant severe dilated cardiomyopathy with conduction defects or atrial/ventricular arrhythmias and a skeletal muscular dystrophy of the quadriceps muscles. Affected members were found to carry the R377H mutation, which was shown by transfection experiments in both muscular and nonmuscular cells to lead to mislocalization of both lamin and emerin (300384). Unlike previously reported cases of LMNA mutations causing dilated cardiomyopathy with neuromuscular involvement, cardiac involvement preceded neuromuscular disease in all affected members. Charniot et al. (2003) suggested that factors other than the R377H mutation influenced phenotypic expression in this family. Sebillon et al. (2003) also reported on this family.
In a German woman who had been diagnosed with LGMD1B, Rudnik-Schoneborn et al. (2007) identified a heterozygous R377H mutation in the LMNA gene. Family history revealed that the patient's paternal grandmother had proximal muscle weakness and died from heart disease at age 52, and a paternal aunt had 'walking difficulties' since youth. The patient's father and 4 cousins all had cardiac disease without muscle weakness ranging from nonspecific 'heart attacks' to dilated cardiomyopathy and arrhythmia. The only living affected cousin also carried the mutation.
