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Pre‐ and postnatal phenotype of 6p25 deletions involving the FOXC1 gene
Author(s) -
Delahaye Andrée,
KhungSavatovsky Suonavy,
Aboura Azzedine,
Guimiot Fabien,
Drunat Séverine,
Alessandri JeanLuc,
Gérard Marion,
Bitoun Pierre,
Boumendil Julien,
Robin Stéphanie,
Huel Chan,
Guilherme Romain,
Serero Stéphane,
Gressens Pierre,
Elion Jacques,
Verloes Alain,
Benzacken Brigitte,
Delezoide AnneLise,
Pipiras Eva
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35548
Subject(s) - haploinsufficiency , biology , phenotype , dysgenesis , breakpoint , genetics , gene duplication , chromosomal translocation , gene , anatomy
FOXC1 deletion, duplication, and mutations are associated with Axenfeld–Rieger anomaly, and Dandy–Walker malformation spectrum. We describe the clinical history, physical findings, and available brain imaging studies in three fetuses, two children, and one adult with 6p25 deletions encompassing FOXC1 . Various combinations of ocular and cerebellar malformations were found. In all three fetuses, necropsy including detailed microscopic assessments of the eyes and brains showed ocular anterior segment dysgenesis suggestive of Axenfeld–Rieger anomaly. Five 6p25 deletions were terminal, including two derived from inherited reciprocal translocations; the remaining 6p25 deletion was interstitial. The size and breakpoints of these deletions were characterized using comparative genomic hybridization arrays. All six deletions included FOXC1 . Our data confirm that FOXC1 haploinsufficiency plays a major role in the phenotype of patients with 6p25 deletions. Histopathological features of Axenfeld–Rieger anomaly were clearly identifiable before the beginning of the third‐trimester of gestation. © 2012 Wiley Periodicals, Inc.