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

Autor: Di Gioia SA; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA., Connors S; Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand., Matsunami N; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA., Cannavino J; Department of Molecular Biology and Neuroscience, and Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 USA., Rose MF; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Medical Genetics Training Program, Harvard Medical School, Boston, Massachusetts 02115, USA.; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.; Broad Institute of M.I.T. and Harvard, Cambridge, Massachusetts 02142, USA., Gilette NM; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA., Artoni P; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA., de Macena Sobreira NL; McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA., Chan WM; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA., Webb BD; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA., Robson CD; Department of Radiology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115, USA., Cheng L; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA., Van Ryzin C; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Ramirez-Martinez A; Department of Molecular Biology and Neuroscience, and Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 USA., Mohassel P; Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1477, USA.; Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Leppert M; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA., Scholand MB; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA., Grunseich C; Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Ferreira CR; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Hartman T; Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine, Hanover, New Hampshire 03755-1404, USA., Hayes IM; Genetic Health Services New Zealand, Auckland City Hospital, Auckland 1142, New Zealand., Morgan T; Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand., Markie DM; Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand., Fagiolini M; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA., Swift A; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Chines PS; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Speck-Martins CE; SARAH Network of Rehabilitation Hospitals, Brasilia 70335-901, Brazil., Collins FS; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1477, USA.; Office of the Director, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Jabs EW; McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA., Bönnemann CG; Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1477, USA.; Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Olson EN; Department of Molecular Biology and Neuroscience, and Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 USA., Carey JC; Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA., Robertson SP; Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand., Manoli I; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1477, USA., Engle EC; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.; Medical Genetics Training Program, Harvard Medical School, Boston, Massachusetts 02115, USA.; Broad Institute of M.I.T. and Harvard, Cambridge, Massachusetts 02142, USA.; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.; Department Ophthalmology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2017 Jul 06; Vol. 8, pp. 16077. Date of Electronic Publication: 2017 Jul 06.
DOI: 10.1038/ncomms16077
Abstrakt: 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 insT/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.
Databáze: MEDLINE