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Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes

Françoise Meire UGent, Isabelle Delpierre, Cecile Brachet, Françoise Roulez, Chrisitan Van Nechel, Fanny Depasse, Catherine Christophe, Björn Menten UGent and Elfride De Baere UGent (2011) MOLECULAR VISION. 17(225-26). p.2072-2079
abstract
Purpose: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported. The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 (PAX6) are known to be implicated in sporadic bilateral ONA. Methods: The individuals reported underwent extensive ophthalmological, endocrinological, and neurologic evaluation, including neuroimaging of the visual pathways. In addition genomewide copy number screening was performed. Results: Here we report an autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with unilateral microphthalmia and ONA in the second generation (II:1), and bilateral ONA in two sibs of the third generation (III: 1; III: 2). No PAX6 mutation was found. Genome wide copy number screening revealed a microdeletion of maximal 363 kb of chromosome 10q23.33q23.33 in all affected individuals (II: 1, III: 1; III: 2) and in unaffected I: 1, containing three genes: exocyst complex component 6 (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode retinoic acid-degrading enzymes. Conclusions: This is the first study reporting an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of neuroimaging in uncovering ONA in microphthalmic patients is demonstrated. Although involvement of other genetic factors cannot be ruled out, our study might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic ONA.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
RETINOIC-ACID, ACID-METABOLIZING ENZYME, OTHERWISE HEALTHY INFANT, HORMONE DEFICIENCY, MURINE DEVELOPMENT, GROWTH-HORMONE, MUTATIONS, CHIASM, MALFORMATIONS, ANOPHTHALMIA
journal title
MOLECULAR VISION
Mol. Vis.
volume
17
issue
225-26
pages
2072 - 2079
Web of Science type
Article
Web of Science id
000293883100002
JCR category
OPHTHALMOLOGY
JCR impact factor
2.205 (2011)
JCR rank
18/56 (2011)
JCR quartile
2 (2011)
ISSN
1090-0535
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2053918
handle
http://hdl.handle.net/1854/LU-2053918
alternative location
http://www.molvis.org/molvis/v17/a226
date created
2012-03-01 09:43:35
date last changed
2017-10-13 06:48:30
@article{2053918,
  abstract     = {Purpose: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported. The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 (PAX6) are known to be implicated in sporadic bilateral ONA. 
Methods: The individuals reported underwent extensive ophthalmological, endocrinological, and neurologic evaluation, including neuroimaging of the visual pathways. In addition genomewide copy number screening was performed. 
Results: Here we report an autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with unilateral microphthalmia and ONA in the second generation (II:1), and bilateral ONA in two sibs of the third generation (III: 1; III: 2). No PAX6 mutation was found. Genome wide copy number screening revealed a microdeletion of maximal 363 kb of chromosome 10q23.33q23.33 in all affected individuals (II: 1, III: 1; III: 2) and in unaffected I: 1, containing three genes: exocyst complex component 6 (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode retinoic acid-degrading enzymes. 
Conclusions: This is the first study reporting an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of neuroimaging in uncovering ONA in microphthalmic patients is demonstrated. Although involvement of other genetic factors cannot be ruled out, our study might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic ONA.},
  author       = {Meire, Fran\c{c}oise and Delpierre, Isabelle and Brachet, Cecile and Roulez, Fran\c{c}oise and Van Nechel, Chrisitan and Depasse, Fanny and Christophe, Catherine and Menten, Bj{\"o}rn and De Baere, Elfride},
  issn         = {1090-0535},
  journal      = {MOLECULAR VISION},
  keyword      = {RETINOIC-ACID,ACID-METABOLIZING ENZYME,OTHERWISE HEALTHY INFANT,HORMONE DEFICIENCY,MURINE DEVELOPMENT,GROWTH-HORMONE,MUTATIONS,CHIASM,MALFORMATIONS,ANOPHTHALMIA},
  language     = {eng},
  number       = {225-26},
  pages        = {2072--2079},
  title        = {Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes},
  url          = {http://www.molvis.org/molvis/v17/a226},
  volume       = {17},
  year         = {2011},
}

Chicago
Meire, Françoise, Isabelle Delpierre, Cecile Brachet, Françoise Roulez, Chrisitan Van Nechel, Fanny Depasse, Catherine Christophe, Björn Menten, and Elfride De Baere. 2011. “Nonsyndromic Bilateral and Unilateral Optic Nerve Aplasia: First Familial Occurrence and Potential Implication of CYP26A1 and CYP26C1 Genes.” Molecular Vision 17 (225-26): 2072–2079.
APA
Meire, F., Delpierre, I., Brachet, C., Roulez, F., Van Nechel, C., Depasse, F., Christophe, C., et al. (2011). Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes. MOLECULAR VISION, 17(225-26), 2072–2079.
Vancouver
1.
Meire F, Delpierre I, Brachet C, Roulez F, Van Nechel C, Depasse F, et al. Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes. MOLECULAR VISION. 2011;17(225-26):2072–9.
MLA
Meire, Françoise, Isabelle Delpierre, Cecile Brachet, et al. “Nonsyndromic Bilateral and Unilateral Optic Nerve Aplasia: First Familial Occurrence and Potential Implication of CYP26A1 and CYP26C1 Genes.” MOLECULAR VISION 17.225-26 (2011): 2072–2079. Print.