Abstract
Purpose :
To report the clinical phenotype associated with pathological sequence variants in the OPN1LW and OPN1MW gene clusters in a Irish family.
Methods :
Genotype was established using Next Generation Sequencing, a revolutionary advance in the identification of disease-associated gene mutations.
As part of our on-going efforts to contribute to a database of Irish inherited retinal degeneration patients (Target 5000) a 73-year-old man, who presented with congenital visual impairment primarily related to day vision, was assessed at the Research Foundation at the Royal Victoria Eye and Ear Hospital, Dublin. Electroretinography studies were carried out on the proband and two great nephews to characterise the phenotype among these family members.
Results :
The proband was diagnosed with Achromatopsia on the basis of electroretinographic (ERG) features consisting of well-preserved rod-isolated responses combined with non-recordable cone-isolated responses. Two of the proband’s great nephews (sons of his sororal niece) were also found to have similar ERG patterns, thus strongly suggesting an X-linked mode of inheritance.
Using NGS, the affected males were confirmed to have potentially pathological sequence variants in both the OPN1LW and OPN1MW gene clusters, (Xq28) mediating long-wavelength (‘red’) and medium wavelength (‘green’) cone opsin production respectively, refining the clinical diagnosis as blue cone monochromatism, an extremely uncommon IRD with a prevalence of approximately 1 in 100,000.
Conclusions :
This Irish family demonstrates an X-linked blue cone monochromatism phenotype associated with potentially pathological sequence variants in the OPN1LW and OPN1MW gene clusters (Xq28).
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.