Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly.

Journal Article (Journal Article)

Genetic linkage, genome mismatch scanning, and analysis of patients with alterations of chromosome 6 have indicated that a major locus for development of the anterior segment of the eye, IRID1, is located at 6p25. Abnormalities of this locus lead to glaucoma. FKHL7 (also called "FREAC3"), a member of the forkhead/winged-helix transcription-factor family, has also been mapped to 6p25. DNA sequencing of FKHL7 in five IRID1 families and 16 sporadic patients with anterior-segment defects revealed three mutations: a 10-bp deletion predicted to cause a frameshift and premature protein truncation prior to the FKHL7 forkhead DNA-binding domain, as well as two missense mutations of conserved amino acids within the FKHL7 forkhead domain. Mf1, the murine homologue of FKHL7, is expressed in the developing brain, skeletal system, and eye, consistent with FKHL7 having a role in ocular development. However, mutational screening and genetic-linkage analyses excluded FKHL7 from underlying the anterior-segment disorders in two IRID1 families with linkage to 6p25. Our findings demonstrate that, although mutations of FKHL7 result in anterior-segment defects and glaucoma in some patients, it is probable that at least one more locus involved in the regulation of eye development is also located at 6p25.

Full Text

Duke Authors

Cited Authors

  • Mears, AJ; Jordan, T; Mirzayans, F; Dubois, S; Kume, T; Parlee, M; Ritch, R; Koop, B; Kuo, WL; Collins, C; Marshall, J; Gould, DB; Pearce, W; Carlsson, P; Enerbäck, S; Morissette, J; Bhattacharya, S; Hogan, B; Raymond, V; Walter, MA

Published Date

  • November 1998

Published In

Volume / Issue

  • 63 / 5

Start / End Page

  • 1316 - 1328

PubMed ID

  • 9792859

Pubmed Central ID

  • PMC1377542

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/302109


  • eng

Conference Location

  • United States