A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.

Journal Article (Journal Article)

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 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.

Full Text

Duke Authors

Cited Authors

  • Di Gioia, SA; Connors, S; Matsunami, N; Cannavino, J; Rose, MF; Gilette, NM; Artoni, P; de Macena Sobreira, NL; Chan, W-M; Webb, BD; Robson, CD; Cheng, L; Van Ryzin, C; Ramirez-Martinez, A; Mohassel, P; Leppert, M; Scholand, MB; Grunseich, C; Ferreira, CR; Hartman, T; Hayes, IM; Morgan, T; Markie, DM; Fagiolini, M; Swift, A; Chines, PS; Speck-Martins, CE; Collins, FS; Jabs, EW; Bönnemann, CG; Olson, EN; Moebius Syndrome Research Consortium, ; Carey, JC; Robertson, SP; Manoli, I; Engle, EC

Published Date

  • July 6, 2017

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 16077 -

PubMed ID

  • 28681861

Pubmed Central ID

  • PMC5504296

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms16077


  • eng

Conference Location

  • England