A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28681861.
- Also identified by DOI 10.1038/ncomms16077 and PMC identifier 5504296.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk<sup>insT/insT</sup> zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits.
Medical subject headings
- Membrane Proteins
- Mobius Syndrome
- Morphogenesis
- Muscle Proteins
- Muscle, Skeletal
- Muscular Diseases
- Mutation
- Myoblasts
- Pierre Robin Syndrome
- Zebrafish Proteins