title: Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome.
abstract: 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 patients present with iris hypoplasia, a prominent Schwalbe line, adhesions between the iris stroma and the iridocorneal angle and increased intraocular pressure. IGDS is characterized by iris hypoplasia, goniodysgenesis and increased intraocular pressure. Each syndrome also presents with non-ocular features including maxillary hypoplasia, micro and anodontia, redundant periumbilical skin, hypospadius (in males), and each has been genetically linked to chromosome 4q25. RIEG1 , the gene responsible for the 4q25 ARS phenotype, recently has been cloned. RIEG1 encodes a novel member of the bicoid class of homeobox proteins known to be active as transcription factors. Mutational analysis has previously detected several mutations in this gene in ARS individuals. We have now detected a mutation in RIEG1 which segregates with the disease phenotype in a family with IGDS. This mutation is a G-->A transition altering an arginine residue to a histidine in a highly conserved location in the second helix of the homeobox of RIEG1. This mutation indicates that IGDS and ARS are allelic variants of the same disorder. This wide variability in clinical consequences of mutations at the RIEG1 4q25 locus implicates the RIEG gene broadly in ocular and craniofacial disorders.
authors.affiliation: Department of Medical Genetics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors.forename: S C
authors.initials: SC
authors.lastname: Kulak
authors.forename: K
authors.initials: K
authors.lastname: Kozlowski
authors.forename: E V
authors.initials: EV
authors.lastname: Semina
authors.forename: W G
authors.initials: WG
authors.lastname: Pearce
authors.forename: M A
authors.initials: MA
authors.lastname: Walter
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000867:Anterior Chamber / Q000002:abnormalities*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007498:Iris / Q000002:abnormalities*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D017354:Point Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C101485:homeobox protein PITX1; C433629:homeobox protein PITX3