Abstract
Frontometaphyseal dysplasia (FMD) is caused by gain-of-function mutations in the X-linked gene FLNA in approximately 50% of patients. Recently we characterized an autosomal dominant form of FMD (AD-FMD) caused by mutations in MAP3K7, which accounts for the condition in the majority of patients who lack a FLNA mutation. We previously also described a patient with a de novo variant in TAB2, which we hypothesized was causative of another form of AD-FMD. In this study, a cohort of 20 individuals with AD-FMD is clinically evaluated. This cohort consists of 15 individuals with the recently described, recurrent mutation (c.1454C>T) in MAP3K7, as well as three individuals with missense mutations that result in substitutions in the N-terminal kinase domain of TGFβ-activated kinase 1 (TAK1), encoded by MAP3K7. Additionally, two individuals have missense variants in the gene TAB2, which encodes a protein with a close functional relationship to TAK1, TAK1-associated binding protein 2 (TAB2). Although the X-linked and autosomal dominant forms of FMD are very similar, there are distinctions to be made between the two conditions. Individuals with AD-FMD have characteristic facial features, and are more likely to be deaf, have scoliosis and ce...Continue Reading
References
May 1, 1966·The American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine·J C Melnick, C F Needles
Oct 1, 1982·Clinical Genetics·J S FitzsimmonsG B Gilbert
Dec 28, 2002·American Journal of Medical Genetics. Part a·Eva MoravaGyörgy Kosztolányi
Jan 31, 2003·Molecular and Cellular Biology·Hideki SanjoShizuo Akira
Mar 4, 2003·Nature Genetics·Stephen P RobertsonUNKNOWN OPD-spectrum Disorders Clinical Collaborative Group
Jul 13, 2006·American Journal of Medical Genetics. Part a·Stephen P RobertsonDeborah Krakow
Aug 24, 2006·European Journal of Human Genetics : EJHG·Stephen P Robertson
Dec 13, 2006·The Journal of Biological Chemistry·Arnaud BesseBryant G Darnay
May 25, 2010·American Journal of Human Genetics·Bernard ThienpontLars Allan Larsen
Jun 17, 2010·The Journal of Clinical Investigation·Matthew B GreenblattLaurie H Glimcher
Apr 23, 2015·American Journal of Medical Genetics. Part a·Hanneke BasartRaoul C Hennekam
Sep 26, 2015·Clinical Genetics·S NaudionP Fergelot
Jul 19, 2016·American Journal of Human Genetics·Emma M WadeStephen P Robertson
Jul 19, 2016·American Journal of Human Genetics·Carine Le GoffValérie Cormier-Daire
Sep 14, 2016·Journal of Medical Genetics·Francisco MartínezCarmen Orellana
Citations
Feb 23, 2018·European Journal of Human Genetics : EJHG·Silvia MorlinoMarco Ritelli
Feb 29, 2020·Human Mutation·Emma M WadeStephen P Robertson
Apr 18, 2020·Cold Spring Harbor Molecular Case Studies·Fatima AbuBakrSaquib A Lakhani
Jan 22, 2020·BMC Cardiovascular Disorders·Jia ChenYanqiu Liu
Jun 30, 2019·Human Mutation·Silvia MorlinoLucia Micale
Dec 30, 2020·American Journal of Medical Genetics. Part a·Ruwangi DissanayakeNirmala D Sirisena
Feb 23, 2021·American Journal of Medical Genetics. Part a·Prabakaran GangadaranAnupriya Kaur
Feb 28, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Lucia MicaleMarco Castori
Aug 31, 2021·European Journal of Human Genetics : EJHG·Aafke EngwerdaWilhelmina S Kerstjens-Frederikse
Sep 25, 2021·American Journal of Medical Genetics. Part a·Mari MinatogawaTomoki Kosho
Oct 31, 2021·Human Genome Variation·Asuka HoriKenichiro Hata
Jun 30, 2021·The Journal of Craniofacial Surgery·Thomas Roland-BillecartJoel Ferri
Nov 7, 2021·Clinical Genetics·Jennifer HansonPenelope E Bonnen