MUTATION IN THE RIEG1 GENE IN PATIENTS WITH IRIDOGONIODYSGENESIS SYNDROME

Axenfeld-Rieger syndrome (ARS) and iridogoniodysgenesis syndrome (IGDS ) are clinically related autosomal dominant disorders which affect the anterior segment of the eye as well as non-ocular structures. ARS pat ients present with iris hypoplasia, a prominent Schwalbe line, adhesio ns between the iris stroma and the iridocorneal angle and increased in traocular pressure. IGDS is characterized by iris hypoplasia, goniodys genesis and increased intraocular pressure. Each syndrome also present s with non-ocular features including maxillary hypoplasia, micro and a nodontia, redundant periumbilical skin, hypospadius (in males), and ea ch has been genetically linked to chromosome 4q25, RIEG1, the gene res ponsible for the 4q25 ARS phenotype, recently has been cloned. RIEG1 e ncodes a novel member of the bicoid class of homeobox proteins known t o be active as transcription factors. Mutational analysis has previous ly detected several mutations in this gene in ARS individuals. We have now detected a mutation in RIEG1 which segregates with the disease ph enotype in a family with IGDS, This mutation is a G-->A transition alt ering an arginine residue to a histidine in a highly conserved locatio n in the second helix of the homeobox of RIEG1, This mutation indicate s that IGDS and ARS are allelic variants of the same disorder. This wi de variability in clinical consequences of mutations at the RIEG1 4q25 locus implicates the RIEG gene broadly in ocular and craniofacial dis orders.