Type

Journal Article

Authors

Sean Ennis
Andrew Green
Sally Lynch
Breandán Kennedy
Regina Regan
Muireann Ní Chróinín
Judith Conroy
Peter Tormey
Jens Erik Nielsen
Derek W Morris
and 7 others

Subjects

Biochemistry

Topics
autosomal recessive colobomatous micro anophthalmia mutation stra6 female genetics microphthalmia matthew wood syndrome anophthalmos phenotype child preschool stra6 protein human male homozygote young adult pathology membrane proteins ireland mutation analysis animals targeted next generation sequencing parasitology consanguinity mws microphthalmos polymorphism single nucleotide chromosome mapping homozygosity mapping coloboma zebrafish infant pedigree isolated humans adult adolescent family

First implication of STRA6 mutations in isolated anophthalmia, microphthalmia and coloboma: a new dimension to the STRA6 phenotype (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.
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Full list of authors on original publication

Sean Ennis, Andrew Green, Sally Lynch, Breandán Kennedy, Regina Regan, Muireann Ní Chróinín, Judith Conroy, Peter Tormey, Jens Erik Nielsen, Derek W Morris and 7 others

Experts in our system

1
Sean Ennis
University College Dublin
Total Publications: 52
 
2
Andrew Green
University College Dublin
Total Publications: 25
 
3
Sally Ann Lynch
University College Dublin
Total Publications: 32
 
4
Breandán N Kennedy
University College Dublin
Total Publications: 46
 
5
Regina Regan
University College Dublin
Total Publications: 10
 
6
Judith Conroy
University College Dublin
Total Publications: 24
 
7
Jens Erik Nielsen
University College Dublin
Total Publications: 27
 
8
Derek Morris
Trinity College Dublin
Total Publications: 156