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Am J Hum Genet. 2015 May 7;96(5):841-9. doi: 10.1016/j.ajhg.2015.04.004.

Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3.

Author information

1
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
2
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Suite R814, Houston, TX 77030-3411, USA.
3
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Division of Genetic Medicine, Seattle Children's Hospital, Seattle, WA 98105, USA.
4
Pediatric Genetics Unit, Department of Pediatrics, School of Medicine, Acibadem University, İstanbul 34752, Turkey.
5
Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
6
Department of Pediatrics, University of Utah, Salt Lake City, UT 84108, USA.
7
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Suite R814, Houston, TX 77030-3411, USA; Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, MS:BCM226, Houston, TX 77030, USA.
8
Departments of Human Genetics and Orthopedic Surgery, University of California, Los Angeles, Los Angeles, CA 90048, USA.
9
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
10
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Division of Genetic Medicine, Seattle Children's Hospital, Seattle, WA 98105, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: mbamshad@uw.edu.

Abstract

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.

PMID:
25957469
PMCID:
PMC4570285
DOI:
10.1016/j.ajhg.2015.04.004
[Indexed for MEDLINE]
Free PMC Article

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