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A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye
journal contribution
posted on 2023-05-16, 13:10 authored by Nishimura, D, Searby, C, Alward, W, Walton, D, Jamie CraigJamie Craig, David MackeyDavid Mackey, Kawase, K, Kanis, A, Patil, S, Stone, E, Sheffield, VMutations in the forkhead transcription-factor gene (FOXC1), have been shown to cause defects of the anterior chamber of the eye that are associated with developmental forms of glaucoma. Discovery of these mutations was greatly facilitated by the cloning and characterization of the 6p25 breakpoint in a patient with both congenital glaucoma and a balanced-translocation event involving chromosomes 6 and 13. Here we describe the identification of novel mutations in the FOXC1 gene in patients with anterior-chamber defects of the eye. We have detected nine new mutations (eight of which are novel) in the FOXC1 gene in patients with anterior-chamber eye defects. Of these mutations, five frameshift mutations predict loss of the forkhead domain, as a result of premature termination of translation. Of particular interest is the fact that two families have a duplication of 6p25, involving the FOXC1 gene. These data suggest that both FOXC1 haploinsufficiency and increased gene dosage can cause anterior-chamber defects of the eye.
History
Publication title
Americal Journal of Human GeneticsVolume
68Pagination
364-372ISSN
0002-9297Department/School
Menzies Institute for Medical ResearchPublisher
University Chicago PressPlace of publication
Chicago, IL, USARepository Status
- Restricted