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

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Title: First implication of STRA6 mutations in isolated anophthalmia, microphthalmia and coloboma: a new dimension to the STRA6 phenotype
Authors: 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.
Permanent link: http://hdl.handle.net/10197/5790
Date: Dec-2011
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
Copyright (published version): 2011 Wiley
Keywords: STRA6Homozygosity mappingMWSMicrophthalmiaMatthew-Wood syndromeAutosomal recessive colobomatous micro-anophthalmiaTargeted next-generation sequencingMutation analysis
DOI: 10.1002/humu.21590
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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