1
SCIEnTIfIC RePoRts | (2018) 8:4498 | DOI:10.1038/s41598-018-22337-2
www.nature.com/scientificreports
Detection of mutations in MYOC,
OPTN, NTF4, WDR36 and CYP1B1
in Chinese juvenile onset open-
angle glaucoma using exome
sequencing
Chukai Huang
1
, Lijing Xie
1
, Zhenggen Wu
1
, Yingjie Cao
1
, Yuqian Zheng
1
, Chi-Pui Pang
1,2
&
Mingzhi Zhang
1
Juvenile onset open-angle glaucoma (JOAG) aects 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
ltering, we identied 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 identied 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.
Glaucoma, the second leading cause of irreversible blindness worldwide
1
, is a group of heterogeneous optic neu-
ropathies characterized by retinal nerve bre layer damage and visual eld defects. e disease is progressive and
leads to permanent visual impairment and even blindness in some patients
2
. Age and high intraocular pressure
(IOP) are the main risk factors. Primary open-angle glaucoma (POAG) is a common form of glaucoma, which
can be further subdivided into juvenile-onset open-angle glaucoma (JOAG) and adult-onset POAG according to
the age of onset
3
. JOAG patients oen have higher intraocular pressure (IOP) and suer from more severe optic
nerve damage than adult-onset POAG patients
4
.
Genetic factors play an important role in the development of glaucoma
5
. Several genes have been identied
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
. e same candidate gene may lead to dierent phenotypes of glaucoma
11
. MYOC is the
rst candidate gene mapped for POAG and has been conrmed to be associated with both POAG and JOAG
12
.
Mutations of OPTN were found in POAG and amyotrophic lateral sclerosis (ALS)
13,14
. CYP1B1 is a PCG gene
but has also been reported in association with JOAG
15,16
. To date, the mutations of known genes only account
for approximately 5% of patients with POAG
17
. Compared with adult-onset POAG, JOAG may be more likely to
be genetically determined and less likely the consequence of environment
16
. Investigation of the POAG genes in
JOAG might provide a good opportunity for understanding the genetic components and heterogeneity of JOAG.
Whole-exome sequencing (WES) is available in commercial service and has been proved to be useful in map-
ping disease genes. It is rapid and comparatively more cost-eective than other genomic technologies, especially
1
Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou,
P. R. China.
2
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong,
P. R. China. Correspondence and requests for materials should be addressed to M.Z. (email: zmz@jsiec.org)
Received: 4 October 2017
Accepted: 16 February 2018
Published: xx xx xxxx
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