English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/188182
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

FAM46A mutations are responsible for autosomal recessive osteogenesis imperfecta

AuthorsDoyard, Mathilde; Bacrot, Séverine; Huber, Céline; Di Rocco, Maja; Goldenberg, Alice; Aglan, Mona; Brunelle, Perrine; Temtamy, Samia; Michot, Caroline; Otaify, Ghada A.; Haudry, Coralie; Castanet, Mireille; Leroux, Julien; Bonnefont, Jean-Paul; Munnich, Arnold; Baujat, Geneviève; Lapunzina, Pablo; Monnot, Sophie; Ruiz-Pérez, Victor L. ; Cormier-Daire, Valérie
Issue Date2018
PublisherBMJ Publishing Group
CitationJournal of Medical Genetics 55(4): 278-284 (2018)
Abstract[Background]: Stüve-Wiedemann syndrome (SWS) is characterised by bowing of the lower limbs, respiratory distress and hyperthermia that are often responsible for early death. Survivors develop progressive scoliosis and spontaneous fractures. We previously identified LIFR mutations in most SWS cases, but absence of LIFR pathogenic changes in five patients led us to perform exome sequencing and to identify homozygosity for a FAM46A mutation in one case [p.Ser205Tyrfs*13]. The follow-up of this case supported a final diagnosis of osteogenesis imperfecta (OI), based on vertebral collapses and blue sclerae.
[Methods and results]: This prompted us to screen FAM46A in 25 OI patients with no known mutations. We identified a homozygous deleterious variant in FAM46A in two affected sibs with typical OI [p.His127Arg]. Another homozygous variant, [p.Asp231Gly], also classed as deleterious, was detected in a patient with type III OI of consanguineous parents using homozygosity mapping and exome sequencing. FAM46A is a member of the superfamily of nucleotidyltransferase fold proteins but its exact function is presently unknown. Nevertheless, there are lines of evidence pointing to a relevant role of FAM46A in bone development. By RT-PCR analysis, we detected specific expression of FAM46A in human osteoblasts andinterestingly, a nonsense mutation in Fam46a has been recently identified in an ENU-derived (N-ethyl-N-nitrosourea) mouse model characterised by decreased body length, limb, rib, pelvis, and skull deformities and reduced cortical thickness in long bones.
[Conclusion]: We conclude that FAM46A mutations are responsible for a severe form of OI with congenital bowing of the lower limbs and suggest screening this gene in unexplained OI forms.
Publisher version (URL)https://doi.org/10.1136/jmedgenet-2017-104999
URIhttp://hdl.handle.net/10261/188182
DOI10.1136/jmedgenet-2017-104999
ISSN0022-2593
E-ISSN1468-6244
Appears in Collections:(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf59,24 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.