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  5. First implication of STRA6 mutations in isolated anophthalmia, microphthalmia and coloboma: a new dimension to the STRA6 phenotype
 
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First implication of STRA6 mutations in isolated anophthalmia, microphthalmia and coloboma: a new dimension to the STRA6 phenotype

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Author(s)
Casey, Jillian 
Kawaguchi, Riki 
Morrissey, Maria 
McGettigan, Paul A. 
Nielsen, Jens Erik 
Conroy, Judith 
Regan, Regina 
Kennedy, Breandán 
Lynch, Sally 
Green, Andrew 
Ennis, Sean 
et al. 
Uri
http://hdl.handle.net/10197/5790
Date Issued
December 2011
Date Available
07T09:32:55Z August 2014
Abstract
Microphthalmia, anophthalmia, and coloboma (MAC) are structural congenital eye malformations that cause a significant proportion of childhood visual impairments. Several disease genes have been identified but do not account for all MAC cases, suggesting that additional risk loci exist. We used single nucleotide polymorphism (SNP) homozygosity mapping (HM) and targeted next-generation sequencing to identify the causative mutation for autosomal recessive isolated colobomatous microanophthalmia (MCOPCB) in a consanguineous Irish Traveller family. We identified a double-nucleotide polymorphism (g.1157G>A and g.1156G>A; p.G304K) in STRA6 that was homozygous in all of the MCOPCB patients. The STRA6 p.G304K mutation was subsequently detected in additional MCOPCB patients, including one individual with Matthew-Wood syndrome (MWS; MCOPS9). STRA6 encodes a transmembrane receptor involved in vitamin A uptake, a process essential to eye development and growth. We have shown that the G304K mutant STRA6 protein is mislocalized and has severely reduced vitamin A uptake activity. Furthermore, we reproduced the MCOPCB phenotype in a zebrafish disease model by inhibiting retinoic acid (RA) synthesis, suggesting that diminished RA levels account for the eye malformations in STRA6 p.G304K patients. The current study demonstrates that STRA6 mutations can cause isolated eye malformations in addition to the congenital anomalies observed in MWS.
Type of Material
Journal Article
Publisher
Wiley
Journal
Human Mutation
Volume
32
Issue
12
Start Page
1417
End Page
1426
Copyright (Published Version)
2011 Wiley
Keywords
  • STRA6

  • Homozygosity mapping

  • MWS

  • Microphthalmia

  • Matthew-Wood syndrome...

  • Autosomal recessive c...

  • Targeted next-generat...

  • Mutation analysis

DOI
10.1002/humu.21590
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
Owning collection
Biomolecular and Biomedical Science Research Collection
Scopus© citations
56
Acquisition Date
Mar 24, 2023
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1664
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Mar 24, 2023
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