title: [Genotype-Phenotype Correlations in Patients with CRB1 Mutations].
abstract: BackgroundMutations in theCRB1gene were identified in patients with early-onset severe retinal dystrophy (EOSRD), childhood-onset and juvenile-onset rod-cone dystrophy. This study describes the phenotypic spectrum of disease-causingCRB1-mutations in the first two decades of life.Materials and MethodsEight patients, aged three months to 20 years, underwent a full comprehensive ophthalmological examination including best corrected visual acuity testing (BCVA), color vision testing, funduscopy, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) recording. Automated and manual retinal layer segmentation of SD-OCT recordings was performed using DIOCTA software. A full-field electroretinography (ffERG, ISCEV Standard) and visual fields were performed in cooperative patients.ResultsFive patients carried mutations causing a loss of the corresponding gene product (splice-mutation, nonsense-mutation, frame-shifting mutation). These patients presented with generally reduced vision in the first months of life that never exceeded 0.04 during the observational period. The sixth patient carried a homozygous missense mutation and reached maximal BCVA 0.05 at the age of 6 years. Two further patients, carrying at least one hypomorphic missense-mutation, presented with better preserved visual function with up to 0.5 at the age of 20 years. The recorded ffERG was below threshold in the majority of patients. Visual fields were severely restricted. The photoreceptor layers were significantly reduced in SD-OCT whenever stratification of retinal layers was possible. The inner nuclear layer thickness increased with progressing retinal degeneration. A-Scan analysis revealed better preservation of the retinal stratification in patients with missense mutations.ConclusionsPatients withCRB1-mutations presented with a severe phenotype with severely reduced visual acuity from birth. Missense mutations with predicted residual function of the gene product were associated with moderate expression of the disease. Severe and progressive restriction of visual fields occurred in the first decade of life. The reduced retinal stratification indicates a general loss of structural integrity of the retinal layers.
authors.affiliation: Klinik und Poliklinik für Augenheilkunde, Justus-Liebig-Universität Gießen, Universitätsklinikum Gießen und Marburg GmbH.
authors.forename: C
authors.initials: C
authors.lastname: Papadopoulou Laiou
authors.affiliation: Klinik und Poliklinik für Augenheilkunde, Justus-Liebig-Universität Gießen, Universitätsklinikum Gießen und Marburg GmbH.
authors.forename: M N
authors.initials: MN
authors.lastname: Preising
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Köln.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bolz
authors.affiliation: Klinik und Poliklinik für Augenheilkunde, Justus-Liebig-Universität Gießen, Universitätsklinikum Gießen und Marburg GmbH.
authors.forename: B
authors.initials: B
authors.lastname: Lorenz
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D058499:Retinal Dystrophies / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D012307:Risk Factors; D013223:Statistics as Topic; D014786:Vision Disorders / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
chemical_list: C448939:CRB1 protein, human; D005136:Eye Proteins; D005819:Genetic Markers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins