Pre- and postnatal phenotype of 6p25 deletions involving the FOXC1 gene.
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.
AP-HP, Hôpital Jean Verdier, Service d'Histologie, Embryologie, et Cytogénétique, Bondy, France. andree.delahaye@jvr.aphp.fr
Andrée
A
Delahaye
Suonavy
S
Khung-Savatovsky
Azzedine
A
Aboura
Fabien
F
Guimiot
Séverine
S
Drunat
Jean-Luc
JL
Alessandri
Marion
M
Gérard
Pierre
P
Bitoun
Julien
J
Boumendil
Stéphanie
S
Robin
Chan
C
Huel
Romain
R
Guilherme
Stéphane
S
Serero
Pierre
P
Gressens
Jacques
J
Elion
Alain
A
Verloes
Brigitte
B
Benzacken
Anne-Lise
AL
Delezoide
Eva
E
Pipiras
D000328:Adult; D000869:Anterior Eye Segment / Q000002:abnormalities / Q000473:pathology; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology*; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003616:Dandy-Walker Syndrome / Q000235:genetics / Q000473:pathology; D005124:Eye Abnormalities / Q000235:genetics / Q000473:pathology*; D015785:Eye Diseases, Hereditary; D005260:Female; D005333:Fetus / Q000473:pathology*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010641:Phenotype; D011247:Pregnancy
C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors