A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.
Nat Commun
; 8: 16077, 2017 07 06.
Article
en En
| MEDLINE
| ID: mdl-28681861
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 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Pierre Robin
/
Músculo Esquelético
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Síndrome de Mobius
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Proteínas de Pez Cebra
/
Mioblastos
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Proteínas de la Membrana
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Morfogénesis
/
Proteínas Musculares
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Enfermedades Musculares
/
Mutación
Límite:
Adult
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Animals
/
Child
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos