Detection of Clinically Relevant Genetic Variants in Chinese Patients With Nanophthalmos by Trio-Based Whole-Genome Sequencing Study
| Autor: | Jian Ge, Denghui Chen, Zhenni Zhao, Nannan Sun, Jianlong Li, Zhigang Fan, Xing Liu, Jiafan Liu, Dandan Zhang, Miao Zhang, He Shuxiang, Xiaoling Zhang, Jiamin Zhang, Zhongwen Li, Congcong Guo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proband Adult Male China Adolescent Biology medicine.disease_cause Genetic analysis Frameshift mutation 03 medical and health sciences symbols.namesake 0302 clinical medicine Asian People medicine Humans Microphthalmos Genetic Testing Child Frameshift Mutation Genetic testing Genetics Mutation medicine.diagnostic_test Whole Genome Sequencing Genetic disorder Membrane Proteins General Medicine Sequence Analysis DNA Middle Aged medicine.disease Stop codon Pedigree 030104 developmental biology 030221 ophthalmology & optometry Mendelian inheritance symbols Female Serine Proteases Transcription Factors |
| Zdroj: | Investigative ophthalmologyvisual science. 60(8) |
| ISSN: | 1552-5783 |
| Popis: | Purpose Nanophthalmos is a rare genetic disorder commonly characterized by a short axial length (AL) and severe hyperopia. Mutations that have been identified through Mendelian genetic analysis can only explain a fraction of nanophthalmic cases. We investigate the clinically relevant genetic variants in nanophthalmos by whole-genome sequencing (WGS), including de novo mutations (DNMs) and inherited mutations. Methods Clinically relevant genetic variants of 11 trios (11 nanophthalmic probands and their unaffected parents) from the Zhongshan Ophthalmic Center, China, were analyzed by WGS. We further screened three trios and 10 sporadic cases to identify the MYRF mutations. Results In two of 11 trios, without evidence of the presence of deleterious inherited autosomal variants, two DNMs of MYRF (c.789delC, p.S264fs and c.789dupC, p.S264fs) were identified in the probands. These loss-of-function DNMs were predicted to result in premature stop codons and protein structure damage in both probands. In addition, deleterious inherited genetic variants in PRSS56 and MFRP were found in eight probands of the other nine trios. Expanded screening found an additional MYRF DNM (c.1433G>C, p.R478P) in one trio and a stop-gain MYRF mutation (c.2956C>T, p.R986X) in one sporadic case, suggesting the recurrence of MYRF mutations in nanophthalmic patients. Conclusions This is the first trio-based WGS study for nanophthalmos, revealing the potential role of DNMs in MYRF and rare inherited genetic variants in PRSS56 and MFRP. The underlying mechanism of MYRF in the development of nanophthalmos needs to be further investigated. |
| Databáze: | OpenAIRE |
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