RAX and anophthalmia in humans: Evidence of brain anomalies.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_7EAACA0C67F1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
RAX and anophthalmia in humans: Evidence of brain anomalies.
Périodique
Molecular Vision
Auteur(s)
Abouzeid H., Youssef M.A., Bayoumi N., Elshakankiri N., Marzouk I., Hauser P., Schorderet D.F.
ISSN
1090-0535 (Electronic)
ISSN-L
1090-0535
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
18
Numéro
150-52
Pages
1449-1456
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
PURPOSE: To report the clinical and genetic study of two families of Egyptian origin with clinical anophthalmia. To further determine the role of the retina and anterior neural fold homeobox gene (RAX) in anophthalmia and associated cerebral malformations.
METHODS: Three patients with clinical anophthalmia and first-degree relatives from two consanguineous families of Egyptian origin underwent full ophthalmologic, general and neurologic examination, and blood tests. Cerebral magnetic resonance imaging (MRI) was performed in the index cases of both families. Genomic DNA was prepared from venous leukocytes, and direct sequencing of all the exons and intron-exon junctions of RAX was performed after PCR amplification.
RESULTS: Clinical bilateral anophthalmia was observed in all three patients. General and neurologic examinations were normal; obesity and delay in psychomotor development were observed in the isolated case. Orbital MRI showed a hypoplastic orbit with present but rudimentary extraocular muscles and normal lacrimal glands. Cerebral MRI showed agenesis of the optic nerves, optic tracts, and optic chiasma. In the index case of family A, the absence of the frontal and sphenoidal sinuses was also noted. In the index case of family B, only the sphenoidal sinus was absent, and there was significant cortical atrophy. The three patients carried a novel homozygous c.543+3A>G mutation (IVS2+3A>G) in RAX. Parents were healthy heterozygous carriers. No mutations were detected in orthodenticle homeobox 2 (OTX2), ventral anterior homeobox 1 (VAX1), or sex determining region Y-box 2 (SOX2).
CONCLUSIONS: This is the first report of a homozygous splicing RAX mutation associated with autosomal recessive bilateral anophthalmia. To our knowledge, only two isolated cases of anophthalmia, three null and one missense case affecting nuclear localization or the DNA-binding homeodomain, have been found to be caused by compound heterozygote RAX mutations. A novel missense RAX mutation was identified in three patients with bilateral anophthalmia and a distinct systemic and neurologic phenotype. The mutation potentially affects splicing of the last exon and is thought to result in a protein that has an aberrant homeodomain and no paired-tail domain. Functional consequences of this change still need to be characterized.
Pubmed
Web of science
Création de la notice
09/07/2012 9:25
Dernière modification de la notice
19/03/2018 11:03
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