RESUMO
Faciogenital dysplasia (FGDY; MIM 305400), or Aarskog syndrome, is an X-linked developmental disorder that adversely affects the formation of specific skeletal structures including elements of the face, the cervical vertebrae, and the distal extremities. FGD1, the gene responsible for faciogenital dysplasia, encodes a guanine nucleotide exchange factor that specifically activates Cdc42, a member of the Rho (Ras homology) family of p21 GTPases. By activating Cdc42, FGD1 stimulates fibroblasts to form filopodia, cytoskeletal elements involved in cellular signaling and migration, and through Cdc42, FGD1 also activates the stress-activated protein kinase/c-Jun N-terminal kinase signaling cascade, a pathway that regulates cell growth and differentiation. Here, we report a detailed characterization of the genomic organization of the FGD1 gene. The FGD1 gene is composed of 18 exons that range in size from 31 to 1240 bp. These exons span over 51 kb of genomic DNA within region Xp11.21. Flanking intronic sequences and the sequence of the 5' and 3' untranslated regions were determined to facilitate the detection of FGDY patient mutations. Analyses show that FGD1 transcripts are differentially spliced; in brain and placenta an alternatively spliced form of the FGD1 transcript removes part of the Cdc42GEF domain to encode a null Cdc42 activator.