Joon-Yong An1, Jae Ho Jung2, Leejee Choi3, Eric D Wieben4, Brian G Mohney5. 1. Department of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Korea. 2. Department of Ophthalmology, Seoul National University College of Medicine, Seoul 03080, Korea. 3. Department of Integrated Biomedical and Life Sciences, College of Health Sciences, Korea University, Seoul 02841, Korea. 4. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA. 5. Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA.
Abstract
PURPOSE: To investigate candidate genes associated with familial strabismus and propose a theory of their interaction in familial strabismus associated with early neurodevelopment. METHODS: Eighteen families, including 53 patients diagnosed with strabismus and 34 unaffected family members, were analyzed. All patients with strabismus and available unaffected family members were evaluated using whole exome sequencing. The primary outcome was to identify rare occurring variants among affected individuals and investigate the evidence of their genetic heterogeneity. These results were compared with exome sequencing analysis to build a comprehensive genetic profile of the study families. RESULTS: We observed 60 variants from 58 genes in 53 patients diagnosed with strabismus. We prioritized the most credible risk variants, which showed clear segregation in family members affected by strabismus. As a result, we found risk variants in four genes (FAT3, KCNH2, CELSR1, and TTYH1) in five families, suggesting their role in development of familial strabismus. In other families, there were several rare genetic variants in affected cases, but we did not find clear segregation pattern across family members. CONCLUSION: Genomic sequencing holds great promise in elucidating the genetic causes of strabismus; further research with larger cohorts or other related approaches are warranted.
PURPOSE: To investigate candidate genes associated with familial strabismus and propose a theory of their interaction in familial strabismus associated with early neurodevelopment. METHODS: Eighteen families, including 53 patients diagnosed with strabismus and 34 unaffected family members, were analyzed. All patients with strabismus and available unaffected family members were evaluated using whole exome sequencing. The primary outcome was to identify rare occurring variants among affected individuals and investigate the evidence of their genetic heterogeneity. These results were compared with exome sequencing analysis to build a comprehensive genetic profile of the study families. RESULTS: We observed 60 variants from 58 genes in 53 patients diagnosed with strabismus. We prioritized the most credible risk variants, which showed clear segregation in family members affected by strabismus. As a result, we found risk variants in four genes (FAT3, KCNH2, CELSR1, and TTYH1) in five families, suggesting their role in development of familial strabismus. In other families, there were several rare genetic variants in affected cases, but we did not find clear segregation pattern across family members. CONCLUSION: Genomic sequencing holds great promise in elucidating the genetic causes of strabismus; further research with larger cohorts or other related approaches are warranted.
Authors: G Drutel; A Héron; M Kathmann; C Gros; S Macé; M Plotkine; J C Schwartz; J M Arrang Journal: Eur J Neurosci Date: 1999-05 Impact factor: 3.386
Authors: Somer L Bishop; Cristan Farmer; Vanessa Bal; Elise B Robinson; A Jeremy Willsey; Donna M Werling; Karoline Alexandra Havdahl; Stephan J Sanders; Audrey Thurm Journal: Am J Psychiatry Date: 2017-03-03 Impact factor: 18.112
Authors: Alaron Lewis; Neil Wilson; George Stearns; Nicolas Johnson; Ralph Nelson; Susan E Brockerhoff Journal: PLoS Genet Date: 2011-08-11 Impact factor: 5.917
Authors: Stephen J Huffaker; Jingshan Chen; Kristin K Nicodemus; Fabio Sambataro; Feng Yang; Venkata Mattay; Barbara K Lipska; Thomas M Hyde; Jian Song; Dan Rujescu; Ina Giegling; Karine Mayilyan; Morgan J Proust; Armen Soghoyan; Grazia Caforio; Joseph H Callicott; Alessandro Bertolino; Andreas Meyer-Lindenberg; Jay Chang; Yuanyuan Ji; Michael F Egan; Terry E Goldberg; Joel E Kleinman; Bai Lu; Daniel R Weinberger Journal: Nat Med Date: 2009-05-03 Impact factor: 53.440