Recurrent Rare Copy Number Variants Increase Risk for Esotropia.

Autor:	Whitman MC; Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States., Di Gioia SA; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, United States., Chan WM; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, United States., Gelber A; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, United States., Pratt BM; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, United States., Bell JL; Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States., Collins TE; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, United States., Knowles JA; Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, New York, United States., Armoskus C; Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, New York, United States., Pato M; Institute for Genomic Health, SUNY Downstate Medical Center, Brooklyn, New York, United States., Pato C; Institute for Genomic Health, SUNY Downstate Medical Center, Brooklyn, New York, United States., Shaaban S; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, United States.; Present address: Department of Pathology and ARUP Laboratories, University of Utah School of Medicine, Salt Lake City, Utah, United States., Staffieri S; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia., MacKinnon S; Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States., Maconachie GDE; Department of Neuroscience, Psychology and Behavior, The University of Leicester Ulverscroft Eye Unit, University of Leicester, Leicester, United Kingdom., Elder JE; Department of Ophthalmology, Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia.; Department of Pediatrics, The University of Melbourne, Parkville, Victoria, Australia., Traboulsi EI; Department of Pediatric Ophthalmology and Strabismus, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States., Gottlob I; Department of Neuroscience, Psychology and Behavior, The University of Leicester Ulverscroft Eye Unit, University of Leicester, Leicester, United Kingdom., Mackey DA; Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.; Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia., Hunter DG; Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States., Engle EC; Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, United States.; Department of Neurology, Harvard Medical School, Boston, Massachusetts, United States.; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2020 Aug 03; Vol. 61 (10), pp. 22.
DOI:	10.1167/iovs.61.10.22
Abstrakt:	Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints. Results: Esotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 × 10-6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95% confidence interval [CI] 5.4-38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95% CI 4.6-25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95% CI 5.4-14.9). Overall, 114 cases (7%) and only 28 controls (0.7%) had one of the three rare duplications. No case nor control had more than one of these three duplications. Conclusions: Rare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia.
Databáze:	MEDLINE
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