title: Protein-altering MYH3 variants are associated with a spectrum of phenotypes extending to spondylocarpotarsal synostosis syndrome.
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.
authors.affiliation: 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.
authors.forename: Raphael
authors.initials: R
authors.lastname: Carapito
authors.affiliation: Service de Génétique Médicale, CHU Rouen, Rouen, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.affiliation: 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.
authors.forename: Nicodème
authors.initials: N
authors.lastname: Paul
authors.affiliation: 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.
authors.forename: Angélique
authors.initials: A
authors.lastname: Pichot
authors.affiliation: Service de Génétique Médicale, CHU Nantes, Nantes, France.
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.affiliation: Service d'Orthopédie Pédiatrique, CHU Nantes, Nantes, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Hamel
authors.affiliation: Département de Pédiatrie, CHU Rouen, Rouen, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Dumant-Forest
authors.affiliation: Département de Chirurgie Pédiatrique, CHU Rouen, Université de Rouen, Rouen, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Leroux
authors.affiliation: Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, INSERM UMR_S 957, Faculté de Médecine, Nantes, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ory
authors.affiliation: Service de Génétique Médicale, CHU Nantes, Nantes, France.|Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, INSERM UMR_S 957, Faculté de Médecine, Nantes, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.affiliation: 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.
authors.forename: Seiamak
authors.initials: S
authors.lastname: Bahram
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000002:abnormalities* / Q000473:pathology; D008297:Male; D009140:Musculoskeletal Diseases / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012600:Scoliosis / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D013580:Synostosis / Q000235:genetics* / Q000473:pathology; D013904:Thoracic Vertebrae / Q000002:abnormalities* / Q000473:pathology
chemical_list: D003598:Cytoskeletal Proteins; C510594:MYH3 polypeptide, human