Griffin Laurie Beth, Farley Frances A, Antonellis Anthony, Keegan Catherine E
Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;; Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;
Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;
Cold Spring Harb Mol Case Stud. 2016 Jul;2(4):a000943. doi: 10.1101/mcs.a000943.
Mutations in FGD1 cause Aarskog-Scott syndrome (AAS), an X-linked condition characterized by abnormal facial, skeletal, and genital development due to abnormal embryonic morphogenesis and skeletal formation. Here we report a novel FGD1 mutation in a family with atypical features of AAS, specifically bilateral upper and lower limb congenital joint contractures and cardiac abnormalities. The male proband and his affected maternal uncle are hemizygous for the novel FGD1 mutation p.Arg921X. This variant is the most carboxy-terminal FGD1 mutation identified in a family with AAS and is predicted to truncate the FGD1 protein at the second to last amino acid of the carboxy-terminal pleckstrin homology (PH) domain. Our study emphasizes the importance of the 3' peptide sequence in the structure and/or function of the FGD1 protein and further demonstrates the need to screen patients with X-linked congenital joint contractures for FGD1 mutations.
FGD1基因的突变会导致Aarskog-Scott综合征（AAS），这是一种X连锁疾病，其特征是由于胚胎形态发生异常和骨骼形成异常而导致面部、骨骼和生殖器发育异常。在此，我们报告了一个具有AAS非典型特征的家系中的一种新型FGD1突变，具体表现为双侧上下肢先天性关节挛缩和心脏异常。男性先证者及其受影响的舅舅对于新型FGD1突变p.Arg921X是半合子。该变异是在一个患有AAS的家系中鉴定出的最靠近羧基末端的FGD1突变，预计会使FGD1蛋白在羧基末端普列克底物蛋白同源性（PH）结构域的倒数第二个氨基酸处截短。我们的研究强调了3'肽序列在FGD1蛋白结构和/或功能中的重要性，并进一步证明了对患有X连锁先天性关节挛缩的患者进行FGD1突变筛查的必要性。
Zotero 插件