Reduced cone photoreceptor function and subtle systemic manifestations in two siblings with loss of SCLT1

• Published in: Ophthalmic genetics Vol. 45; no. 1; p. 95
• Main Authors: Grudzinska Pechhacker, Monika K, Molnar, Anna, Pekkola Pacheco, Nadja, Thonberg, Håkan, Querat, Laurence, Birkeldh, Ulrika, Nordgren, Ann, Lindstrand, Anna
• Format: Journal Article
• Language: English
• Published: England 01.02.2024
• Subjects: Child; Ciliopathies - pathology; Electroretinography; Humans; Male; Mutation; Pedigree; Phenotype; Retinal Cone Photoreceptor Cells - pathology; Retinal Dystrophies - pathology; Siblings; Sodium Channels; Strabismus; SCLT1; cone dysfunction; retinal degeneration; Bardet-Biedl syndrome; ciliopathy
• ISSN: 1744-5094
• DOI: 10.1080/13816810.2023.2215332

The sodium channel and clathrin linker 1 gene ( ) has been involved in the pathogenesis of various ciliopathy disorders such as Bardet-Biedl syndrome, orofaciodigital syndrome type IX, and Senior-Løken syndrome. Detailed exams are warranted to outline all clinical features. Here, we present a family with a milder phenotype of -related disease. Comprehensive eye examination including fundus images, OCT, color vision, visual fields and electroretinography were performed. Affected individuals were assessed by a pediatrician and a medical geneticist for systemic features of ciliopathy. Investigations included echocardiography, abdominal ultrasonography, blood work-up for diabetes, liver and kidney function. Genetic testing included NGS retinal dystrophy panel, segregation analysis and transcriptome sequencing. Two male children, age 10 and 8 years, were affected with attention deficit hyperactivity disorder (ADHD), obesity and mild photophobia. The ophthalmic exam revealed reduced best-corrected visual acuity (BCVA), strabismus, hyperopia, astigmatism and moderate red-green defects. Milder changes suggesting photoreceptors disease were found on retinal imaging. Electroretinogram confirmed cone photoreceptors dysfunction. Genetic testing revealed a homozygous likely pathogenic, splice-site variant in gene NM_144643.3: c.1439 + 1del in the proband and in the affected brother. The unaffected parents were heterozygous for the variant. Transcriptome sequencing showed retention of intron 16 in the proband. In this report, we highlight the importance of further extensive diagnostics in patients with unexplained reduced vision, strabismus, refractive errors and ADHD spectrum disorders. -related retinal degeneration is very rare and isolated reduced function of cone photoreceptors has not previously been observed.