RT Journal Article
A1 da Palma, Mariana Matioli
A1 Motta, Fabiana Louise
A1 Gomes, Caio Perez
A1 Salles, Mariana Vallim
A1 Pesquero, João Bosco
A1 Sallum, Juliana Maria Ferraz
T1 Synonymous Variant in the CHM Gene Causes Aberrant Splicing in Choroideremia
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2020
DO 10.1167/iovs.61.2.38
VO 61
IS 2
SP 38
OP 38
SN 1552-5783
AB    Choroideremia is an inherited retinal degeneration caused by 280 different pathogenic variants in the CHM gene. Only one silent/synonymous variant (c.1359C>T; p.(Ser453=)) has been reported and was classified as inconclusive based on in silico analysis. This study elucidates the pathogenicity of this variant also found in a Brazilian patient.    Ophthalmological examinations such as color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, and macular integrity assessment microperimetry were performed. The subjects' total RNA was extracted from peripheral blood cells. cDNA was synthesized and the amplification between exon 10 and 14 of the CHM mRNA was performed. The amplification products were sequenced by Sanger sequencing and the results were aligned to the reference sequence.    The synonymous variant c.1359C>T p.(Ser453=) in the CHM gene is associated with an error in mRNA processing, leading preferentially to production of an aberrant transcript without exon 11 (p.(Gln451Phefs*3)). This anomalous mRNA production is related to typical choroideremia phenotype.    These molecular findings reinforce the need for more detailed investigation of silent variants in patients with well-defined phenotype of retinal dystrophies. Molecular and clinical findings provided evidence that c.1359C>T (p.(Gln451Phefs*3)) in CHM should be considered a disease-causing variant.  
RD 5/27/2020
UL https://doi.org/10.1167/iovs.61.2.38