Title: Expanding the Spectrum of FOXC1 and PITX2 Mutations and Copy Number Changes in Patients with Anterior Segment Malformations
Authors: D'haene, Barbara ×
Meire, Francoise
Claerhout, Ilse
Kroes, Hester Y
Plomp, Astrid
Arens, Yvonne H
de Ravel de l'Argentière, Thomy
Casteels, Ingele
De Jaegere, Sarah
Hooghe, Sally
Wuyts, Wim
van den Ende, Jenneke
Roulez, Francoise
Veenstra-Knol, Hermine E
Oldenburg, Rogier A
Giltay, Jacques
Verheij, Joke B
de Faber, Jan-Tjeerd
Menten, Bjorn
De Paepe, Anne
Kestelyn, Philippe
Leroy, Bart P
De Baere, Elfride #
Issue Date: Jan-2011
Publisher: Association for Research in Vision and Ophthalmology
Series Title: Investigative Ophthalmology & Visual Science vol:52 issue:1 pages:324-333
Abstract: Purpose: Anterior segment dysgenesis (ASD) comprises a heterogeneous group of developmental abnormalities affecting several structures of the anterior segment of the eye. The main purpose of this study was to assess the proportion of FOXC1 and PITX2 mutations and copy number changes in 80 probands with ASD. Methods: The patients were examined for FOXC1 and PITX2 copy number changes and mutations using MLPA and direct sequencing. Subsequently, the identified copy number changes were fine-mapped using high-resolution microarrays. In the remaining mutation negative patients sequencing of the FOXC1 and PITX2 3' untranslated regions (UTRs) and three other candidate genes (P32, PDP2 and FOXC2) was performed. Results: We identified thirteen FOXC1 and eight PITX2 mutations, accounting for 26% of the cases (21/80). In addition, six FOXC1 and five PITX2 deletions were found, explaining 14% of the cases (11/80). The smallest FOXC1 and PITX2 deletions are 5.4 kb and 1.6 kb in size respectively. Six patients carrying FOXC1 deletions presented with variable extra-ocular phenotypic features such as hearing defects (4/6) and mental retardation (2/6). No further genetic defects could be found in the remaining mutation negative patients. Conclusions: FOXC1 and PITX2 genetic defects explain 40% of our large ASD cohort. We considerably extended the current spectrum of intragenic FOXC1 and PITX2 mutations, fine-mapped the identified copy number changes, identified the smallest FOXC1 and PITX2 deletions reported so far, and emphasized the need for dedicated copy number screening of the FOXC1 and PITX2 genomic landscape. This study is unique in that we simultaneously screened for sequence changes and copy number changes in both genes.
ISSN: 0146-0404
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Research Group Ophthalmology
× corresponding author
# (joint) last author

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