Homozygosity for the dominant MYOT c.179C>T (p.Ser60Phe) mutation causes a more severe, late-onset proximal and distal muscular dystrophy phenotype compared to heterozygosity.
Case Report
Does homozygosity for the dominant MYOT c.179C>T mutation cause a more severe disease phenotype compared to heterozygosity?
This report demonstrates that dominant MYOT mutations can exhibit a dose effect, causing a more severe muscular dystrophy phenotype in homozygosity.
Most myotilinopathy patients present with a dominant late onset distal phenotype and myofibrillar pathology, although the first MYOT mutation in a family reported to have LGMD phenotype. We report here a French family affected with a late onset proximal and distal muscle weakness and myofibrillar myopathy on muscle pathology, in which the siblings known to be clinically affected were homozygous for the c.179C>T (p.Ser60Phe) myotilin gene mutation. One subjectively asymptomatic member of the family was heterozygous for this mutation. This is the first report of a family with patients being homozygous for a known dominant MYOT mutation. Dominant negative mutations are generally considered not to cause a more severe disease in homozygosity, but our data clearly demonstrate the existence of dominant MYOT mutations with a possible dose effect causing a more severe disease phenotype in homozygosity in the spectrum of myofibrillar myopathies (MFM).
Rudolf et al. (Fri,) conducted a case report in Myofibrillar myopathy / Muscular Dystrophy. Homozygosity for the c.179C>T (p.Ser60Phe) myotilin gene mutation vs. Heterozygosity for the mutation was evaluated on Disease severity and phenotype. Homozygosity for the dominant MYOT c.179C>T (p.Ser60Phe) mutation causes a more severe, late-onset proximal and distal muscular dystrophy phenotype compared to heterozygosity.