| SP F-017 |
| Hidden Genetic Variations in PAX6-Associated Aniridia revealed by Whole Genome Sequencing
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| Department of Ophthalmology, Yonsei University College of Medicine, Gangnam Severance Hospital
Department of Laboratory Medicine, Yonsei University College of Medicine
Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine |
| Jinu Han, Seung-Tae Lee, Hyun Taek Lim |
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목적 : To find hidden pathogenic variants associated with aniridia who were negative for conventional Sanger sequencing or targeted next-generation sequencing (NGS) with multiplex ligation probe amplification (MLPA).
방법 : Three patients with classic aniridia, who were regarded as unsolved after PAX6 Sanger sequencing or targeted NGS accompanied with MLPA analysis, were recruited in 2 university-based hospitals. Whole genome sequencing was performed using HiSeq X 10. Variants were filtered and prioritized by Genomiser, CADD (combined annotation dependent depletion), FATHMM-MKL (Functional annotation through hidden Markov models-multiple kernel learning) and in-depth clinical review.
결과 : All 3 patients had a family history of aniridia, infantile onset-nystagmus, foveal hypoplasia. No patients had mental retardation, ataxia and autism. Two patients were men and all patients were of single ethnicity (Korean). Nonsense mutation c.19G>T:p.G7X was found in one patients, which was missed by prior Sanger sequencing with unknown technical reason leading to incorrect base calling. Two 5’ untranslated regions (UTR) c.-133_-132delTA and c.-52+5G>A variants were prioritized in 2 patients by Genomiser, CADD, FATHMM-MKL algorithms.
결론 : These findings suggest that WGS can identify pathogenic non-coding regulatory variant in PAX6 gene. Functional studies using luciferase reporter assay will be needed to confirm the pathogenicity of these regulatory variants.
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