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Retinitis pigmentosa caused by mutations in the ciliary MAK gene is relatively mild and is not associated with
Ramon A C van Huet1, Anna M Siemiatkowska, Riza K Özgül
1Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
Purpose:
Defects in MAK, encoding a protein localized to the photoreceptor connecting cilium, have recently been associated with autosomal recessive retinitis pigmentosa (RP). The aim of this study is to describe our detailed clinical observations in patients with MAK-associated RP, including an assessment of syndromic symptoms frequently observed in ciliopathies.
Methods:
In this international collaborative study, 11 patients carrying nonsense or missense mutations in MAK were clinically evaluated, including extensive assessment of the medical history, slit-lamp biomicroscopy, ophthalmoscopy, kinetic perimetry, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), autofluorescence imaging and fundus photography. Additionally, we used a questionnaire to evaluate the presence of syndromic features and tested the olfactory function.
Results:
MAK-associated RP is not associated with syndromic features, not even with subclinical dysfunction of the olfactory apparatus. All patients experienced typical RP symptoms of night blindness followed by visual field constriction. Symptoms initiated between childhood and the age of 43 (mean: 23 years). Although some patients experienced vision loss, the visual acuity remained normal in most patients. ERG and ophthalmoscopy revealed classic RP characteristics, and SD-OCT demonstrated thinning of the overall retina, outer nuclear layer and photoreceptor-pigment epithelium complex.
Conclusion:
Nonsense and missense mutations in MAK give rise to a non-syndromic recessive RP phenotype without apparent extra-ocular features. When compared to other retinal ciliopathies, MAK-associated RP appears to be relatively mild and shows remarkable resemblance to RP1-associated RP, which could be explained by the close functional relation of these proteins.
Insights
Mutations in the MAK gene cause a mild, non-syndromic form of autosomal recessive retinitis pigmentosa (RP) without extra-ocular features. This condition resembles RP1-associated RP due to the proteins' functional relationship.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- Defects in the MAK gene, encoding a protein in the photoreceptor connecting cilium, are linked to autosomal recessive retinitis pigmentosa (RP).
- Ciliopathies, a group of disorders affecting cilia, can present with syndromic features.
Purpose of the Study:
- To detail clinical findings in patients with MAK-associated RP.
- To assess for syndromic symptoms common in ciliopathies.
Main Methods:
- Clinical evaluation of 11 patients with MAK mutations (nonsense or missense).
- Included medical history, ophthalmic examinations (slit-lamp, funduscopy, perimetry, ERG, SD-OCT, autofluorescence), and olfactory function testing.
- Syndromic features assessed via questionnaire.
Main Results:
- MAK-associated RP did not present with syndromic features or olfactory dysfunction.
- Patients experienced typical RP symptoms: night blindness and visual field constriction, starting between childhood and age 43.
- Most patients maintained normal visual acuity; ERG and ophthalmoscopy showed classic RP; SD-OCT revealed retinal thinning.
Conclusions:
- MAK gene mutations result in a non-syndromic recessive RP phenotype.
- No apparent extra-ocular manifestations were observed.
- MAK-associated RP is relatively mild and clinically similar to RP1-associated RP, likely due to functional protein interactions.
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