A novel heterozygous MYOT deletion (Tyr4_His9del) causes an early-onset myofibrillar myopathy with a distal phenotype, supported by zebrafish models showing severe motor impairments.
Case Report
A novel in-frame deletion in MYOT (Tyr4_His9del) causes early-adult onset distal myopathy, supported by zebrafish models showing sarcomeric disorganization.
Missense mutations in MYOT encoding the sarcomeric Z-disk protein myotilin cause three main myopathic phenotypes including proximal limb-girdle muscular dystrophy, spheroid body myopathy, and late-onset distal myopathy. We describe a family carrying a heterozygous MYOT deletion (Tyr4His9del) that clinically was characterized by an early-adult onset distal muscle weakness and pathologically by a myofibrillar myopathy (MFM). Molecular modeling of the full-length myotilin protein revealed that the 4-YERPKH-9 amino acids are involved in local interactions within the N-terminal portion of myotilin. Injection of in vitro synthetized mutated human MYOT RNA or of plasmid carrying its cDNA sequence in zebrafish embryos led to muscle defects characterized by sarcomeric disorganization of muscle fibers and widening of the I-band, and severe motor impairments. We identify MYOT novel Tyr4His9 deletion as the cause of an early-onset MFM with a distal myopathy phenotype and provide data supporting the importance of the amino acid sequence for the structural role of myotilin in the sarcomeric organization of myofibers.
Guglielmi et al. (Tue,) conducted a case report in Myofibrillar myopathy / distal myopathy. MYOT deletion (Tyr4_His9del) was evaluated on Muscle defects and motor impairments. A novel heterozygous MYOT deletion (Tyr4_His9del) causes an early-onset myofibrillar myopathy with a distal phenotype, supported by zebrafish models showing severe motor impairments.