CLEC3B is a novel causative gene for macular-retinal dystrophy
Exome sequencing was performed to determine putative disease-causing genes in patients with inherited macular disorders confirmed by comprehensive ophthalmic examinations. Five multigenerational families diagnosed with autosomal dominant maculoretinopathy” were found to carry a pathogenic variant in a new gene, CLEC3B. This study recruited twelve affected individuals and seven healthy relatives from five large Japanese families in a small village in Miyazaki with an undetermined diagnosis of inherited macular disorder. According to their family history, there were multiple affected members spanning several generations in each family with 70% of female individuals. The inherited pattern was mostly consistent with an autosomal dominant pattern, as indicated in the familial pedigrees. Attached is WES data of six affected individuals (F1: IV-24, F1: VI-2, F2: IV-2, F3: IV-2, F3: V-3, and F5: V-10) and three unaffected siblings (F3: V-4, F3: V-6 and F5: IV-13) from five Japanese families.
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Exome sequencing and bioinformatics analysis Genomic DNA was extracted from peripheral blood using the Genomic DNA Extraction Kit (Invitrogen, Grand Island, NY, US). Exome sequencing data from six patients with inherited macular disorders and three healthy relatives, were analyzed for shared rare variants. Exome sequencing was conducted on the HiSeq2500 platform(Illumina, USA) as previously described.21 Variants in 84 reported genes known to be associated with retinitis pigmentosa were manually filtered.22 Population allele frequency was performed using the Genome Aggregation Databases(gnomAD), 1000 Genomes databases, ESP6500, etc. Variant effect prediction was assessed by SIFT, Polyphen2, MutationTaster, etc. Sanger verification was performed on all patients and healthy controls who enrolled in this study.