TY - JOUR
T1 - Retinitis pigmentosa caused by mutations in the ciliary MAK gene is relatively mild and is not associated with apparent extra-ocular features
AU - van Huet, Ramon A C
AU - Siemiatkowska, Anna M
AU - Özgül, Riza K
AU - Yücel, Didem
AU - Hoyng, Carel B
AU - Banin, Eyal
AU - Blumenfeld, Anat
AU - Rotenstreich, Ygal
AU - Riemslag, Frans C C
AU - den Hollander, Anneke I
AU - Theelen, Thomas
AU - Collin, Rob W J
AU - van den Born, L Ingeborgh
AU - Klevering, B Jeroen
N1 - © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
PY - 2015/2
Y1 - 2015/2
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Codon, Nonsense
KW - Electroretinography
KW - Female
KW - Fluorescein Angiography
KW - Humans
KW - Male
KW - Middle Aged
KW - Mutation, Missense
KW - Pedigree
KW - Phenotype
KW - Photoreceptor Connecting Cilium/metabolism
KW - Protein-Serine-Threonine Kinases/genetics
KW - Retinitis Pigmentosa/genetics
KW - Surveys and Questionnaires
KW - Tomography, Optical Coherence
KW - Visual Field Tests
KW - Young Adult
U2 - 10.1111/aos.12500
DO - 10.1111/aos.12500
M3 - Article
C2 - 25385675
SN - 1755-375X
VL - 93
SP - 83
EP - 94
JO - Acta Ophthalmologica
JF - Acta Ophthalmologica
IS - 1
ER -