Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies

• Published in: International journal of molecular sciences 2019-09, Vol.20 (19), p.4854
• Main Authors: Boulanger-Scemama, Elise, Mohand-Saïd, Saddek, El Shamieh, Said, Démontant, Vanessa, Condroyer, Christel, Antonio, Aline, Michiels, Christelle, Boyard, Fiona, Saraiva, Jean-Paul, Letexier, Mélanie, Sahel, José-Alain, Zeitz, Christina, Audo, Isabelle
• Format: Article
• Language: English
• Subjects: Abnormalities; Adolescent; Adult; Alleles; Atrophy; Biomarkers; Child; Child, Preschool; Cone-Rod Dystrophies - diagnosis; Cone-Rod Dystrophies - genetics; Congenital diseases; Cords; Electroretinography; Female; Fundus Oculi; Genes; Genetic Association Studies - methods; Genetic counseling; Genetic Predisposition to Disease; Genetics; Genotype; Genotypes; Guanylate cyclase 1; Heterogeneity; High-Throughput Nucleotide Sequencing; Human genetics; Human health and pathology; Humans; Infant; Life Sciences; Male; Medical imaging; Middle Aged; Mutation; Next-generation sequencing; Optical Coherence Tomography; Patients; Phenotype; Phenotypes; Retina; Retinal Cone Photoreceptor Cells - metabolism; Retinal degeneration; Retinal Dystrophies - diagnosis; Retinal Dystrophies - genetics; Retinal images; Sensory Organs; Sequences; Tomography, Optical Coherence; Young Adult
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20194854

Phenotypes observed in a large cohort of patients with cone and cone-rod dystrophies (COD/CORDs) are described based on multimodal retinal imaging features in order to help in analyzing massive next-generation sequencing data. Structural abnormalities of 58 subjects with molecular diagnosis of COD/CORDs were analyzed through specific retinal imaging including spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (BAF/IRAF). Findings were analyzed with the underlying genetic defects. A ring of increased autofluorescence was mainly observed in patients with and mutations (33% and 22% of cases respectively). "Speckled" autofluorescence was observed with mutations in three different genes ( 64%; and , 18% each). Peripapillary sparing was only found in association with mutations in , although only present in 40% of such genotypes. Regarding SD-OCT, specific outer retinal abnormalities were more commonly observed in particular genotypes: focal retrofoveal interruption and mutations (50%), foveal sparing and mutations (50%), and outer retinal atrophy associated with hyperreflective dots and mutations (69%). This study outlines the phenotypic heterogeneity of COD/CORDs hampering statistical correlations. A larger study correlating retinal imaging with genetic results is necessary to identify specific clinical features that may help in selecting pathogenic variants generated by high-throughput sequencing.