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Aniridia (
MIM: 106210)
Aniridia
is a congenital, hereditary, bilateral iris hypoplasia that may be associated
with other ocular defects. It describes an extreme form of iris hypoplasia in
which the iris appears absent on superficial clinical examination. This usually
occurs in both eyes. Aniridia may be broadly divided into hereditary and
sporadic forms. Hereditary Aniridia is usually transmitted in an autosomal
dominant manner, although rarer autosomal recessive forms (such as Gillespie
syndrome) have also been reported. Aniridia is caused by mutation in the paired
box gene-6 (PAX6). Approximately one third of all cases of Aniridia are
sporadic and these are often found to have cytogenetically detectable deletions
involving 11p13 that contains the PAX6 gene.
Congenital Hereditary Endothelial Dystrophy
Congenital
endothelial dystrophy (CHED) can be inherited either as an autosomal dominant
disease (CHED1;
MIM: 121700)
or as autosomal recessive form (CHED2;
MIM: 217700).
CHED1, associated with mutations in CHED1 gene, is a rare disorder
involving degeneration of the endothelial (inner) layer of the cornea and is
characterized by a markedly opaque cornea due to stromal edema secondary to
defective endothelial cells. CHED2 is a severe and rare
bilateral corneal
disorder that presents at birth or shortly thereafter, characterized by corneal
opacification and nystagmus.
The clinical diagnosis is based on the presence of a diffused corneal oedema in
the absence of any other anterior segment abnormality.
It is associated with mutations in SLC4A11 gene. In
India
there is a high frequency of CHED2, possibly related to
consanguineous marriages.
This database presently holds the relevant data for Congenital Hereditary Endothelial Dystrophy 2 (CHED2) only.
Glaucoma
Glaucoma
is a heterogeneous group of optic neuropathies with a complex genetic basis. It
is the second largest blinding disorder after cataract. Recent reports estimate
that there would be ~60.5 million people with primary glaucoma in 2010 and 79.6
million by 2020 resulting in bilateral blindness. According to the W.H.O
report, 9% of the total blind population in Indian subcontinent (India,
Bangladesh, Nepal and Pakistan) is glaucomatous. According to the latest
estimate approximately 12 million people will be affected with glaucoma by 2010
in India. Glaucoma can broadly be classified into three major groups: (i)
primary open angle glaucoma (POAG;
MIM: 137760);
(ii) primary acute closed angle glaucoma (PACG; MIM: Not Available); and
(iii) primary congenital glaucoma (PCG;
MIM: 231300).
Primary Open Angle Glaucoma (POAG),
the commonest form of glaucoma, is described as optic nerve damage from
multiple possible causes that is chronic and progresses over time, with a loss
of optic nerve fibers that is characteristic of the disease. In addition POAG
is characterized by open anterior chamber angles, visual field abnormalities,
and intraocular pressure (IOP) that is too high for the continued health of the
eye. Till date, 25 loci have been found to be linked with POAG but only three
underlying genes have been identified viz. Myocilin, Optineurin and
WDR36. CYP1B1 mutations are also implicated in certain POAG cases.
Primary Congenital Glaucoma (PCG)
is usually diagnosed at birth or shortly thereafter. It is characterized by
improper development of the eye's drainage channel (called trabecular
meshwork). Because of this, the channel that normally drains the fluid (called
aqueous humor) from inside the eye does not function properly ultimately
leading to high IOP. Till date 4 loci have been found to be linked with PCG.
One of the underlying genes has been identified as CYP1B1, which is
primarily implicated towards development of PCG. Apart from CYP1B1,
mutations in FOXC1 and LTBP2 have also been identified in a few
PCG cases.
Primary Angle Closure Glaucoma (PACG)
is associated with a physically obstructed anterior chamber angle. It is
caused by contact between the iris and trabecular meshwork, which
in turn obstructs the outflow of the aqueous humor from
the eye.
Very little information is available regarding genetic factors related to PACG.
Literature reports the association of few polymorphic variants with PACG, which
suggests the possible role of underlying genetic variations in PACG.
Retinitis Pigmentosa (
MIM: 268000)
Retinitis
pigmentosa (RP) is a group of inherited disorders characterized by progressive
peripheral vision loss and night vision difficulties (nyctalopia) that can lead
to central vision loss. RP constitutes many retinal dystrophies and retinal
pigment epithelium (RPE) dystrophies caused by molecular defects in more than
100 different genes. RP can be passed on by all types of inheritance: 20-25% is
autosomal dominant, 15-20% is autosomal recessive, and 5-10% is X linked, while
the remaining 45-50% is found in patients without any known affected relatives.
The incident seems to be about one in every 4,000-5000 worldwide.
In
South India, Retinitis pigmentosa in the urban
population has been recorded to be approximately 1 in 930 persons, while 1 in
372 of rural subjects had the disorder.
The database presently holds the relevant data for RLBP1,ABCA4, RHO, TULP1, RP1, RPE65 and RPF31 genes.
Congenital cataract (
MIM: 601286)
Here,
the characteristic opacification of lenses are diagnosed at birth. In 75% of
cases of congenital cataract hereditary cataract is passed from one generation
to the next in autosomal dominant fashion. There are also a number of rare
hereditary syndromes where the occurrence of cataract is associated with some
systemic illness. Evidence for linkage was found with gamma-crystallin-1
(CRYG1) gene and also CRYGD genes. Mutations in a few other genes like LIM2 and
GJ8 are also associated with congenital cataract.
The
database presently holds the relevant data for LIM2, GJ8 and
CRYGS genes.
Usher Syndrome
Usher
syndrome
is a rare disorder that is a leading cause of deaf-blindness.
It is associated with a mutation in any one of 10
candidate genes. Usher
syndrome is incurable at present. In this disease, deafness is associated with
a defective inner ear, and the vision loss is associated with retinitis
pigmentosa (RP), a degeneration of the retinal cells. Usher syndrome has three
clinical subtypes, denoted as I, II and III in decreasing order of severity.
People with Usher I (
MIM: 276900)
are born
profoundly deaf, begin to lose their vision in the first decade of life and
have problems with balance in movement. Different subtypes of Usher I can be
caused by mutations in any one of several different genes that function in the
development and maintenance of inner ear structures and transmit sound and
motion signals to the brain eg: CDH23,
MYO7A,
PCDH15, USH1C, and
USH1G. People with Usher II are also born deaf, but do not seem to have
noticeable problems with balance; they also begin to lose their vision later.
Different subtypes of Usher syndrome type II
(MIM: Not available)
may be caused by mutations in any of three different genes:
USH2A, GPR98 and
DFNB31. People with Usher syndrome III are not born deaf, but
experience a gradual loss of their hearing and vision; they may or may not have
balance difficulties. Mutations in only one gene, the
CLRN1 gene, have been linked to Usher syndrome type III (
MIM: 276902).
In India, Usher syndrome is the second most common
cause of deafness.
Considering the studies done in India to date, this database presently holds the relevant data for Usher Syndrome type I only caused by mutations in MYO7A.
Oculocutaneous Albinism
Oculocutaneous
albinism (OCA) is a heterogeneous group of congenital disorders characterized
by hypopigmentation of skin, hair, and eyes associated with other developmental
ocular defects. OCA patients are often considered as legally blind and in
India, it is one of the 4 major causes of childhood blindness. Long-term sun
exposure greatly increases the risk of skin damage and an aggressive form of
skin cancer called melanoma, in people with this condition. Mutations in genes
regulating the multistep process of melanin biosynthesis cause this spectrum of
disorders. The four classical types of oculocutaneous albinism are designated
as OCA1 (OCA1A: MIM: 203100 and OCA1B: MIM: 606952), OCA2 (
MIM: 203200),
OCA3 (
MIM: 203290)
and OCA4 (MIM: 606574) caused by
TYR, OCA2, TYRP1 and
SLC45A2 genes, respectively. OCA1 is
characterized by white hair, very pale skin, and light-colored irises. OCA2 and
OCA4 have overlapping clinical features (a creamy white color and hair may be
light yellow, blond, or light brown) that are generally less severe than OCA1.
OCA3 affected individuals have reddish-brown skin, ginger or red hair and hazel
or brown irises with milder vision abnormalities than the other forms of OCA.
Overall, an estimated 1 in 20,000-30,000 people worldwide are born with
oculocutaneous albinism however, the frequency differs from country to country.
In India, OCA1 is the most prevalent type of OCA followed by OCA2.
Microspheropakia (
MIM: 251750)
This
is a congenital, apparently autosomal recessive, usually bilateral, condition
in which the crystalline lens is smaller than normal and spherical in shape. It
may give rise to lenticular myopia, subluxation or glaucoma. It may occur
independently or it may be associated with the Weill-Marchesani syndrome or
more rarely with Marfan's syndrome, Peter's anomaly or congenital rubella.
Microspherophakia can be caused by mutations in the LTBP2 gene.
Leber congenital amaurosis (
MIM: 204100 )
Leber congenital amaurosis is a rare inherited eye
disease that appears either at birth or in the first few months
of life, and affects around 1 in 80,000 of the population, typically
characterized by nystagmus, sluggish or no pupillary responses, and
severe vision loss or blindness. LCA is an autosomal recessive
disorder thought to be caused by abnormal development of photoreceptor cells.
OMIM currently recognizes 11 types of LCA, of which presently this database
contains information for LCA type 2 and LCA type 5 caused by the mutations in
the RPE65 and
LCA5 genes.
Gelatinous drop-like corneal dystrophy (
MIM: 204870 )
Gelatinous
drop-like corneal dystrophy is an
autosomal recessive disorder caused by homozygous or compound heterozygous
mutation in the M1S1 gene. It is characterized by severe corneal amyloidosis.
The disease clinically manifests in the first decade of life and gradually
progresses leading to severely impaired visual acuity by the third decade.
Lattice corneal dystrophy Type I (
MIM: 122200)
Lattice corneal dystrophy,
type I is an autosomal dominant eye disorder caused by mutation in the gene
encoding keratoepithelin (TGFBI). It is characterized by grayish cotton
threads-like lines mainly limited to a zone between the center of the cornea
and the periphery, usually not extending to the limbus. The intervening cornea
is relatively clear. The disease appears in adolescence and progresses to
severe visual impairment by the fifth or sixth decade.
Keratoconus (
MIM: 605020 )
Keratoconus
is a degenerative disorder of the eye in which structural changes within the
cornea cause it to thin and change to a more conical shape than its normal
gradual curve, thereby causing substantial distortion of vision with multiple
images, streaking and sensitivity to light all often reported by the patient.
It is generally diagnosed in the patient's adolescent years and attains its
most severe state in the twenties and thirties. The incidence of keratoconus is
1 in 2,000 in the general population. Keratoconus is associated with mutations
in the VSX1 gene and is inherited in both autosomal dominant and recssive
modes.
Granular corneal dystrophy Type I (
MIM: 121900 )
Granular corneal dystrophy,
type I is an autosomal dominant eye disorder caused by heterozygous mutation in
the gene encoding keratoepithelin (TGFBI). There is corneal opacity in a
disc-shaped area in the center, but the peripheral cornea is usually clear and
the intervening cornea between granules is clear.
Leber congenital amaurosis 2 (
MIM: 204100)
Leber
congenital amaurosis 2 is an autosomal recessive early-onset eye disorder
caused by mutations in the
RPE65
gene.
Patients suffer from retinal dystrophy characterized by
profound vision loss, nystagmus, severe retinal dysfunction and other
associated eye features.
Macular Corneal Dystrophy (
MIM: 217800)
Macular
corneal dystrophy is an autosomal recessive disorder affecting the cornea,
caused by mutations in the CHST6 gene (MIM: 605294). It is a progressive
disorder characterized by minute, gray, punctate corneal opacities with
reduction of corneal sensitivity. Most patients suffer from painful attacks
with photophobia, foreign body sensations and recurrent erosions.
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