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- Title
Clinical and genetic findings in TRPM1‐related congenital stationary night blindness.
- Authors
Iosifidis, Christos; Liu, Jingshu; Gale, Theodora; Ellingford, Jamie M.; Campbell, Christopher; Ingram, Stuart; Chandler, Kate; Parry, Neil R. A.; Black, Graeme C.; Sergouniotis, Panagiotis I.
- Abstract
Purpose: Congenital stationary night blindness (CSNB) is a heterogeneous group of Mendelian retinal disorders that present in childhood. Biallelic variants altering the protein‐coding region of the TRPM1 gene are one of the commonest causes of CSNB. Here, we report the clinical and genetic findings in 10 unrelated individuals with TRPM1‐retinopathy. Methods: Study subjects were recruited through a tertiary clinical ophthalmic genetic service at Manchester, UK. All participants underwent visual electrodiagnostic testing and panel‐based genetic analysis. Results: Study subjects had a median age of 8 years (range: 3–20 years). All probands were myopic and had electroretinographic findings in keeping with complete CSNB. Notably, three probands reported no night vision problems. Fourteen different disease‐associated TRPM1 variants were detected. One individual was homozygous for the NM_001252024.2 (TRPM1):c.965 + 29G>A variant and a mini‐gene assay highlighted that this change results in mis‐splicing and premature protein termination. Additionally, two unrelated probands who had CSNB and mild neurodevelopmental abnormalities were found to carry a 15q13.3 microdeletion. This copy number variant encompasses seven genes, including TRPM1, and was encountered in the heterozygous state and in trans with a missense TRPM1 variant in each case. Conclusion: Our findings highlight the importance of comprehensive genomic analysis, beyond the exons and protein‐coding regions of genes, for individuals with CSNB. When this characteristic retinal phenotype is accompanied by extraocular findings (including learning and/or behavioural difficulties), a 15q13.3 microdeletion should be suspected. Focused analysis (e.g. microarray testing) is recommended to look for large‐scale deletions encompassing TRPM1 in patients with CSNB and neurodevelopmental abnormalities.
- Subjects
DNA copy number variations; RETINAL diseases; BLINDNESS; GENOMICS; GENETIC testing; GAIN-of-function mutations; MYOPIA; GENETIC code; DIABETIC retinopathy
- Publication
Acta Ophthalmologica (1755375X), 2022, Vol 100, Issue 6, pe1332
- ISSN
1755-375X
- Publication type
Article
- DOI
10.1111/aos.15186