Should Patients with Kearns-Sayre Syndrome and Corneal Endothelial Failure Be Genotyped for a TCF4 Trinucleotide Repeat, Commonly Associated with Fuchs Endothelial Corneal Dystrophy?
| Autor: | Marketa Tesarova, Pavlina Skalicka, Alice E. Davidson, Nicole Anteneova, Amanda N. Sadan, Monika Chylova, Petra Liskova, Tomas Honzik, Helena Jahnová, Lubica Dudakova |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Corneal endothelium Pathology medicine.medical_specialty corneal dystrophy genetic structures Genotype Corneal dystrophy Kearns-Sayre Syndrome endothelial failure QH426-470 DNA Mitochondrial Article Cataract Kearns–Sayre syndrome Kearns-Sayre syndrome corneal endothelium CTG18.1 TCF4 exome sequencing symbols.namesake Transcription Factor 4 Ptosis Trinucleotide Repeats Exome Sequencing Genetics medicine Humans Genetics (clinical) Exome sequencing Sequence Deletion Sanger sequencing business.industry Endothelium Corneal Fuchs' Endothelial Dystrophy medicine.disease eye diseases Phenotype symbols sense organs medicine.symptom Chronic progressive external ophthalmoplegia business Trinucleotide repeat expansion |
| Zdroj: | Genes Genes; Volume 12; Issue 12; Pages: 1918 Genes, Vol 12, Iss 1918, p 1918 (2021) |
| ISSN: | 2073-4425 |
| Popis: | The aim of this study was to describe the ocular phenotype in a case with Kearns-Sayre syndrome (KSS) spectrum and to determine if corneal endothelial cell dysfunction could be attributed to other known distinct genetic causes. Herein, genomic DNA was extracted from blood and exome sequencing was performed. Non-coding gene regions implicated in corneal endothelial dystrophies were screened by Sanger sequencing. In addition, a repeat expansion situated within an intron of TCF4 (termed CTG18.1) was genotyped using the short tandem repeat assay. The diagnosis of KSS spectrum was based on the presence of ptosis, chronic progressive external ophthalmoplegia, pigmentary retinopathy, hearing loss, and muscle weakness, which were further supported by the detection of ~6.5 kb mtDNA deletion. At the age of 33 years, the proband’s best corrected visual acuity was reduced to 0.04 in the right eye and 0.2 in the left eye. Rare ocular findings included marked corneal oedema with central corneal thickness of 824 and 844 µm in the right and left eye, respectively. No pathogenic variants in the genes, which are associated with corneal endothelial dystrophies, were identified. Furthermore, the CTG18.1 genotype was 12/33, which exceeds a previously determined critical threshold for toxic RNA foci appearance in corneal endothelial cells. |
| Databáze: | OpenAIRE |
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