Pasteris N G, Cadle A, Logie L J, Porteous M E, Schwartz C E, Stevenson R E, Glover T W, Wilroy R S, Gorski J L
Department of Human Genetics, University of Michigan, Ann Arbor 48109-0688.
Cell. 1994 Nov 18;79(4):669-78. doi: 10.1016/0092-8674(94)90552-5.
Faciogenital dysplasia (FGDY), also known as Aarskog-Scott syndrome, is an X-linked developmental disorder characterized by disproportionately short stature and by facial, skeletal, and urogenital anomalies. Molecular genetic analyses mapped FGDY to chromosome Xp11.21. To clone this gene, YAC clones spanning an FGDY-specific translocation breakpoint were isolated. An isolated cDNA, FGD1, is disrupted by the breakpoint, and FGD1 mutations cosegregate with the disease. FGD1 codes for a 961 amino acid protein that has strong homology to Rho/Rac guanine nucleotide exchange factors (GEFs), contains a cysteine-rich zinc finger-like region, and, like the RasGEF mSos, contains two potential SH3-binding sites. These results provide compelling evidence that FGD1 is responsible for FGDY and suggest that FGD1 is a Rho/RacGEF involved in mammalian development.
面生殖器发育异常（FGDY），也称为阿斯克格-斯科特综合征，是一种X连锁发育障碍，其特征为身材比例失调性矮小以及面部、骨骼和泌尿生殖系统异常。分子遗传学分析将FGDY定位到X染色体p11.21。为了克隆该基因，分离出了跨越FGDY特异性易位断点的酵母人工染色体（YAC）克隆。一个分离出的cDNA，FGD1，被该断点破坏，且FGD1突变与疾病共分离。FGD1编码一种961个氨基酸的蛋白质，该蛋白质与Rho/Rac鸟嘌呤核苷酸交换因子（GEF）具有高度同源性，包含一个富含半胱氨酸的锌指样区域，并且与RasGEF mSos一样，包含两个潜在的SH3结合位点。这些结果提供了令人信服的证据，证明FGD1是导致FGDY的原因，并表明FGD1是一种参与哺乳动物发育的Rho/RacGEF。
