RGD Reference Report - First implication of STRA6 mutations in isolated anophthalmia, microphthalmia, and coloboma: a new dimension to the STRA6 phenotype. - Rat Genome Database

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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  Sun, Hui  McGettigan, Paul  Nielsen, Jens E  Conroy, Judith  Regan, Regina  Kenny, Elaine  Cormican, Paul  Morris, Derek W  Tormey, Peter  Chróinín, Muireann Ní  Kennedy, Breandan N  Lynch, SallyAnn  Green, Andrew  Ennis, Sean 
Citation: Casey J, etal., Hum Mutat. 2011 Dec;32(12):1417-26. doi: 10.1002/humu.21590. Epub 2011 Sep 29.
RGD ID: 155631284
Pubmed: PMID:21901792   (View Abstract at PubMed)
PMCID: PMC3918001   (View Article at PubMed Central)
DOI: DOI:10.1002/humu.21590   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
STRA6HumanIsolated Microphthalmia with Coloboma  IAGP DNA:missense mutation:CDS:p.G204K (human)RGD 
Stra6RatIsolated Microphthalmia with Coloboma  ISOSTRA6 (Homo sapiens)DNA:missense mutation:CDS:p.G204K (human)RGD 
Stra6MouseIsolated Microphthalmia with Coloboma  ISOSTRA6 (Homo sapiens)DNA:missense mutation:CDS:p.G204K (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
STRA6HumanAnophthalmia  IAGP DNA:missense mutation:CDS:p.G204KRGD 
STRA6HumanColoboma  IAGP DNA:missense mutation:CDS:p.G204KRGD 
STRA6HumanMicrophthalmia  IAGP DNA:missense mutation:CDS:p.G204KRGD 
Objects Annotated

Genes (Rattus norvegicus)
Stra6  (signaling receptor and transporter of retinol STRA6)

Genes (Mus musculus)
Stra6  (stimulated by retinoic acid gene 6)

Genes (Homo sapiens)
STRA6  (signaling receptor and transporter of retinol STRA6)


Additional Information