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Bi-allelic MYH3 loss-of-function variants cause a lethal form of contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B.
Kamien, Benjamin; Clayton, Joshua S; Lee, Han-Shin; Abeysuriya, Disna; McNamara, Elyshia; Martinovic, Jelena; Gonzales, Marie; Melki, Judith; Ravenscroft, Gianina.
Afiliación
  • Kamien B; Genetic Services of Western Australia, Perth, WA, Australia; School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
  • Clayton JS; Harry Perkins Institute, Centre for Medical Research, University of Western Australia, Nedlands, WA, Australia.
  • Lee HS; Maternal Fetal Medicine, King Edward Memorial Hospital, Subiaco, WA, Australia.
  • Abeysuriya D; Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, WA, Australia.
  • McNamara E; Harry Perkins Institute, Centre for Medical Research, University of Western Australia, Nedlands, WA, Australia.
  • Martinovic J; Unit of Embryo-Fetal Pathology, AP-HP, Antoine Béclère Hospital, Clamart, France.
  • Gonzales M; Unité d'Embryofoetopathologie, Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, Assistance Publique Hopitaux de Paris, Paris, France.
  • Melki J; Institut National de la Santé et de la Recherche Médicale (Inserm), UMR-1195, Université Paris Saclay, Le Kremlin Bicêtre, France.
  • Ravenscroft G; Harry Perkins Institute, Centre for Medical Research, University of Western Australia, Nedlands, WA, Australia. Electronic address: gina.ravenscroft@uwa.edu.au.
Neuromuscul Disord ; 32(5): 445-449, 2022 05.
Article en En | MEDLINE | ID: mdl-35484034
Arthrogryposis is a consequence of reduced fetal movements and arises due to environmental factors or underlying genetic defects, with extensive genetic heterogeneity. In many instances, the genes responsible are involved in neuromuscular function. Missense variants in the gene encoding embryonic myosin heavy chain (MYH3) usually cause distal arthrogryposis. Recently, mono-allelic or bi-allelic MYH3 variants have been associated with contractures, pterygia, and spondylocarpotarsal fusion syndrome 1 (CPSFS1A and CPSFS1B). Here we describe three fetuses presenting in the second trimester with a lethal form of arthrogryposis and pterygia and harbouring bi-allelic variants in MYH3. One proband was compound heterozygous for a missense change and an extended splice site variant, a second proband had a homozygous frameshift variant, and a third proband was homozygous for a nonsense variant. Minigene assays performed on the first fetus showed that the missense and extended splice site variants resulted in aberrant splicing, likely resulting in near complete loss of full-length MYH3 transcript. This study shows that loss of MYH3 is associated with a lethal arthrogryposis phenotype and highlights the utility of minigene assays to assess splicing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artrogriposis / Anomalías Cutáneas / Sinostosis / Contractura Límite: Humans Idioma: En Revista: Neuromuscul Disord Asunto de la revista: NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artrogriposis / Anomalías Cutáneas / Sinostosis / Contractura Límite: Humans Idioma: En Revista: Neuromuscul Disord Asunto de la revista: NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido