Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3
| Autor: | Jessica X. Chong, Lindsay C. Burrage, Anita E. Beck, Colby T. Marvin, Margaret J. McMillin, Kathryn M. Shively, Tanya M. Harrell, Kati J. Buckingham, Carlos A. Bacino, Mahim Jain, Yasemin Alanay, Susan A. Berry, John C. Carey, Richard A. Gibbs, Brendan H. Lee, Deborah Krakow, Jay Shendure, Deborah A. Nickerson, Michael J. Bamshad, Gonçalo R. Abecasis, Peter Anderson, Elizabeth Marchani Blue, Marcus Annable, Brian L. Browning, Christina Chen, Jennifer Chin, Gregory M. Cooper, Colleen P. Davis, Christopher Frazar, Zongxiao He, Preti Jain, Gail P. Jarvik, Guillaume Jimenez, Eric Johanson, Goo Jun, Martin Kircher, Tom Kolar, Stephanie A. Krauter, Niklas Krumm, Suzanne M. Leal, Daniel Luksic, Sean McGee, Patrick O’Reilly, Bryan Paeper, Karynne Patterson, Marcos Perez, Sam W. Phillips, Jessica Pijoan, Christa Poel, Frederic Reinier, Peggy D. Robertson, Regie Santos-Cortez, Tristan Shaffer, Cindy Shephard, Deborah L. Siegel, Joshua D. Smith, Jeffrey C. Staples, Holly K. Tabor, Monica Tackett, Jason G. Underwood, Marc Wegener, Gao Wang, Marsha M. Wheeler, Qian Yi |
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| Přispěvatelé: | Acibadem University Dspace |
| Rok vydání: | 2015 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Intellectual and Developmental Disabilities (IDD) Biology Myosins medicine.disease_cause Medical and Health Sciences 03 medical and health sciences Camptodactyly 0302 clinical medicine Rare Diseases Osteogenesis Clinical Research Report Myosin medicine Genetics Humans Genetic Predisposition to Disease Exome Genetics(clinical) skin and connective tissue diseases University of Washington Center for Mendelian Genomics Genetics (clinical) Exome sequencing 030304 developmental biology Arthrogryposis Pediatric Genetics & Heredity 0303 health sciences Mutation Genetic heterogeneity nutritional and metabolic diseases High-Throughput Nucleotide Sequencing Biological Sciences medicine.disease Brain Disorders Cytoskeletal Proteins Congenital Structural Anomalies Multiple pterygium syndrome medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | American journal of human genetics, vol 96, iss 5 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2015.04.004 |
| Popis: | Multiple pterygium syndrome (MPS) is a phenotypically and genetically heterogeneous group of rare Mendelian conditions characterized by multiple pterygia, scoliosis, and congenital contractures of the limbs. MPS typically segregates as an autosomal-recessive disorder, but rare instances of autosomal-dominant transmission have been reported. Whereas several mutations causing recessive MPS have been identified, the genetic basis of dominant MPS remains unknown. We identified four families affected by dominantly transmitted MPS characterized by pterygia, camptodactyly of the hands, vertebral fusions, and scoliosis. Exome sequencing identified predicted protein-altering mutations in embryonic myosin heavy chain (MYH3) in three families. MYH3 mutations underlie distal arthrogryposis types 1, 2A, and 2B, but all mutations reported to date occur in the head and neck domains. In contrast, two of the mutations found to cause MPS in this study occurred in the tail domain. The phenotypic overlap among persons with MPS, coupled with physical findings distinct from other conditions caused by mutations in MYH3, suggests that the developmental mechanism underlying MPS differs from that of other conditions and/or that certain functions of embryonic myosin might be perturbed by disruption of specific residues and/or domains. Moreover, the vertebral fusions in persons with MPS, coupled with evidence of MYH3 expression in bone, suggest that embryonic myosin plays a role in skeletal development. |
| Databáze: | OpenAIRE |
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