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Title: | Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical phenotype |
Authors: | WADE, Emma M.; JENKINS, Zandra A.; DANIEL, Philip B.; MORGAN, Tim; ADDOR, Marie C.; ADES, Lesley C.; BERTOLA, Debora; BOHRING, Axel; CARTER, Erin; CHO, Tae-Joon; GEUS, Christa M. de; DUBA, Hans-Christoph; FLETCHER, Elaine; HADZSIEV, Kinga; HENNEKAM, Raoul C. M.; KIM, Chong A.; KRAKOW, Deborah; MORAVA, Eva; NEUHANN, Teresa; SILLENCE, David; SUPERTI-FURGA, Andrea; VEENSTRA-KNOL, Hermine E.; WIECZOREK, Dagmar; WILSON, Louise C.; MARKIE, David M.; ROBERTSON, Stephen P. |
Citation: | AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v.173, n.7, p.1739-1746, 2017 |
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 TGF beta-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 cervical fusions, and have a cleft palate. Furthermore, there are features only found in AD-FMD in our review of the literature including valgus deformity of the feet and predisposition to keloid scarring. Finally, intellectual disability is present in a small number of subjects with AD-FMD but has not been described in association with X-linked FMD. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MPE Artigos e Materiais de Revistas Científicas - HC/ICr Artigos e Materiais de Revistas Científicas - LIM/36 |
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