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Eur J Hum Genet. 2016 Dec;24(12):1746-1751. doi: 10.1038/ejhg.2016.84. Epub 2016 Jul 6.

Protein-altering MYH3 variants are associated with a spectrum of phenotypes extending to spondylocarpotarsal synostosis syndrome.

Author information

1
Plateforme GENOMAX, Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
2
Service de Génétique Médicale, CHU Rouen, Rouen, France.
3
Service de Génétique Médicale, CHU Nantes, Nantes, France.
4
Service d'Orthopédie Pédiatrique, CHU Nantes, Nantes, France.
5
Département de Pédiatrie, CHU Rouen, Rouen, France.
6
Département de Chirurgie Pédiatrique, CHU Rouen, Université de Rouen, Rouen, France.
7
Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, INSERM UMR_S 957, Faculté de Médecine, Nantes, France.

Abstract

Spondylocarpotarsal synostosis syndrome (SCT) is a rare Mendelian disorder (OMIM #272460) characterized by prenatal vertebral fusion, scoliosis, short stature and carpal and tarsal synostosis. SCT is typically known as an autosomal recessive disease caused by variants in the FLNB gene. The genetic basis of the rarer cases of vertical transmissions remains unknown. In two independent families with symptoms related to autosomal dominant SCT, we identified - by exome sequencing - two protein-altering variants in the embryonic myosin heavy chain 3 (MYH3) gene. As MYH3 variants are also associated with distal arthrogryposis (DA1, DA2A, DA2B) and autosomal dominant multiple pterygium syndromes (MPS), the present study expands the phenotypic spectrum of MYH3 variants to autosomal dominant SCT. Vertebral, carpal and tarsal fusions observed in both families further confirm that MYH3 plays a key role in skeletal development.

PMID:
27381093
PMCID:
PMC5117933
DOI:
10.1038/ejhg.2016.84
[Indexed for MEDLINE]
Free PMC Article

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