Abstract
Juvenile onset open-angle glaucoma (JOAG) affects patients before 40 years of age, causing high intraocular pressure and severe optic nerve damage. To expand the mutation spectrum of the causative genes in JOAG, with a view to identify novel disease-causing mutations, we investigated MYOC, OPTN, NTF4, WDR36 and CYP1B1 in a cohort of 67 unrelated Chinese JOAG patients. Whole exome sequencing was used to identify possible pathogenic mutations, which were further excluded in normal controls. After sequencing and the use of a database pipeline, as well as predictive assessment filtering, we identified a total of six mutations in three genes, MYOC, OPTN and CYP1B1. Among them, 2 heterozygous mutations in MYOC (c. 1109C > T, p. (P370L); c. 1150G > C, p. (D384H)), 2 heterozygous mutations in OPTN (c. 985A > G, p.(R329G); c. 1481T > G, p. (L494W)) and 2 homozygous mutations in CYP1B1 (c. 1412T > G, p.(I471S); c. 1169G > A, p.(R390H)) were identified as potentially causative mutations. No mutation was detected in NTF4 or WDR36. Our results enrich the mutation spectra and frequencies of MYOC, OPTN and CYP1B1 in JOAG among the Chinese population. Further studies are needed to address the pathogenicity of each of the mutations detected in this study.
Highlights
Glaucoma, the second leading cause of irreversible blindness worldwide[1], is a group of heterogeneous optic neuropathies characterized by retinal nerve fibre layer damage and visual field defects
No MYOC or OPTN potential disease causing mutations were detected in 125 controls, while two heterozygous mutations of CYP1B1 (c. 1169G > A p. (R390H)) were found in controls (Table 1)
5.97% (4/67) of Juvenile onset open-angle glaucoma (JOAG) patients carry a heterozygous mutation in MYOC
Summary
The second leading cause of irreversible blindness worldwide[1], is a group of heterogeneous optic neuropathies characterized by retinal nerve fibre layer damage and visual field defects. Several genes have been identified to be associated with POAG, primary congenital glaucoma (PCG) and JOAG, including myocilin (MYOC)[6]; optineurin (OPTN)[7]; WD repeat domain 36 (WDR36)[8]; neurotrophin 4 (NTF4)[9]; and cytochrome P450 family 1, subfamily B(CYP1B1)[10]. Whole-exome sequencing (WES) is available in commercial service and has been proved to be useful in mapping disease genes. It is rapid and comparatively more cost-effective than other genomic technologies, especially www.nature.com/scientificreports/. We performed WES on 67 Chinese JOAG patients to detect the full spectra of variants in MYOC, OPTN, NTF4, WDR36 and CYP1B1, with a view to identify novel disease-causing mutations for JOAG
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
