Document Type
Journal Article
Publication Date
7-2017
Journal
Nature Communications
Volume
8
DOI
10.1038/ncomms16077
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 mymkinsT/insT zebrafish in vivocan 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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
DiGioia, S., Connors, S., Matsunami, N., Cannavino, J., Rose, M., Gillette, N., Gropman, A., & +several additional authors (2017). A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nature Communications, 8 (). http://dx.doi.org/10.1038/ncomms16077
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Macmillan Publishers Ltd. Nature Communications