Aniridia
Encyclopedia
Aniridia is the absence of the iris
. Aniridia usually involves both eyes. It can be congenital or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular
and optic nerve hypoplasia
, cataract
, and cornea
l changes. Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus
, amblyopia
, buphthalmos
, and cataract
. Aniridia in some individuals is associated with kidney nephroblastoma (Wilms tumor) or with mental retardation and cerebellar ataxia
(Gillespie syndrome
).
gene (named for its PAired boX status), whose gene product helps regulate a cascade of other genetic processes involved in the development of the eye (as well as other nonocular structures). This PAX6 gene is around 95% similar to the pax gene found in zebrafish, a creature whose ancestors diverged from human evolutionary development around 400 million years ago. Thus the PAX6 gene is highly conserved across evolution
ary lineages.
Defects in the PAX6 gene cause aniridia-like ocular defects in mice
(as well as Drosophila
). Aniridia is a heterozygous disorder, meaning that only one of the two chromosome 11 copies is affected. When both copies are altered (homozygous condition), the result is a uniformly fatal condition with near complete failure of entire eye formation. In 2001, two cases of homozygous aniridia patients were reported; the fetuses died prior to birth and had severe brain damage. In mice, homozygous small eye defect (mouse Pax-6) leads to loss of the eyes and nose and the murine fetuses suffer severe brain damage.
) have also been reported. Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). These patients often also have genitourinary abnormalities and mental retardation
(WAGR syndrome
).
Several different mutations may affect the PAX6 gene. Some mutations appear to inhibit gene function more than others, with subsequent variability in the severity of the disease. Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have foveal hypoplasia, and retain relatively normal vision
. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder phenotype
.
AN Aniridia and absent patella Aniridia, microcornea, and spontaneously reabsorbed cataract Aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome)
) testing for PAX6 gene mutations (by sequencing
of the entire coding region
and deletion/duplication analysis) is available for isolated aniridia and the Gillespie syndrome. For the WAGR syndrome, high-resolution cytogenetic analysis and fluorescence in situ hybridization (FISH) can be utilized to identify deletions within chromosome band 11p13, where both the PAX6 and WT1 genes are located.
Neethirajan G, Solomon A, Krishnadas SR, Vijayalakshmi P, Sundaresan P. (2009). "Genotype/phenotype association in Indian congenital aniridia".Indian J Pediatr 76 (5):513-517.PMID: 19390808
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
. Aniridia usually involves both eyes. It can be congenital or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular
Macular hypoplasia
Macular hypoplasia, also known as fovea hypoplasia, is a rare medical condition involving the underdevelopment of the macula, a small area on the retina responsible for seeing in detail. Macular hypoplasia is often associated with albinism.-External links:*...
and optic nerve hypoplasia
Optic nerve hypoplasia
Optic nerve hypoplasia is a medical condition arising from the underdevelopment of the optic nerve. This condition is the most common congenital optic nerve anomaly. The optic disc appears abnormally small, because not all the optic nerve axons have developed properly...
, cataract
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
, and cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
l changes. Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus
Nystagmus
Nystagmus is a condition of involuntary eye movement, acquired in infancy or later in life, that may result in reduced or limited vision.There are two key forms of Nystagmus: pathological and physiological, with variations within each type. Nystagmus may be caused by congenital disorders,...
, amblyopia
Amblyopia
Amblyopia, also known as lazy eye, is a disorder of the visual system that is characterized by a vision deficiency in an eye that is otherwise physically normal, or out of proportion to associated structural abnormalities of the eye...
, buphthalmos
Buphthalmos
Buphthalmos is a medical term that describes enlargement of the eyeball and is most commonly seen in infants and young children. It is sometimes referred to as buphthalmia . It usually appears in the newborn period or the first 3 months of life...
, and cataract
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
. Aniridia in some individuals is associated with kidney nephroblastoma (Wilms tumor) or with mental retardation and cerebellar ataxia
Cerebellar ataxia
Cerebellar ataxia is a form of ataxia originating in the cerebellum.-References:...
(Gillespie syndrome
Gillespie syndrome
Gillespie syndrome, also called aniridia, cerebellar ataxia and mental deficiency and Gillespie's syndrome II, is a rare genetic disorder. The disorder is characterized by partial aniridia , ataxia , and, in most cases, intellectual disability...
).
PAX6
The AN2 region of the short arm of chromosome 11 (11p13) includes the PAX6PAX6
Paired box protein Pax-6 also known as aniridia type II protein or oculorhombin is a protein that in humans is encoded by the PAX6 gene.- Function :PAX6 is a member of the Pax gene family...
gene (named for its PAired boX status), whose gene product helps regulate a cascade of other genetic processes involved in the development of the eye (as well as other nonocular structures). This PAX6 gene is around 95% similar to the pax gene found in zebrafish, a creature whose ancestors diverged from human evolutionary development around 400 million years ago. Thus the PAX6 gene is highly conserved across evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
ary lineages.
Defects in the PAX6 gene cause aniridia-like ocular defects in mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...
(as well as Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
). Aniridia is a heterozygous disorder, meaning that only one of the two chromosome 11 copies is affected. When both copies are altered (homozygous condition), the result is a uniformly fatal condition with near complete failure of entire eye formation. In 2001, two cases of homozygous aniridia patients were reported; the fetuses died prior to birth and had severe brain damage. In mice, homozygous small eye defect (mouse Pax-6) leads to loss of the eyes and nose and the murine fetuses suffer severe brain damage.
Types
Aniridia may be broadly divided into hereditary and sporadic forms. Hereditary aniridia is usually transmitted in an autosomal dominant manner (each offspring has a 50% chance of being affected), although rare autosomal recessive forms (such as Gillespie syndromeGillespie syndrome
Gillespie syndrome, also called aniridia, cerebellar ataxia and mental deficiency and Gillespie's syndrome II, is a rare genetic disorder. The disorder is characterized by partial aniridia , ataxia , and, in most cases, intellectual disability...
) have also been reported. Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). These patients often also have genitourinary abnormalities and mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
(WAGR syndrome
WAGR syndrome
WAGR syndrome is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumour , Aniridia , Genitourinary anomalies, and mental Retardation...
).
Several different mutations may affect the PAX6 gene. Some mutations appear to inhibit gene function more than others, with subsequent variability in the severity of the disease. Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have foveal hypoplasia, and retain relatively normal vision
Visual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or vision...
. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
.
AN Aniridia and absent patella Aniridia, microcornea, and spontaneously reabsorbed cataract Aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome)
Mutational Analysis
Molecular (DNADNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
) testing for PAX6 gene mutations (by sequencing
Sequencing
In genetics and biochemistry, sequencing means to determine the primary structure of an unbranched biopolymer...
of the entire coding region
Coding region
The coding region of a gene, also known as the coding sequence or CDS, is that portion of a gene's DNA or RNA, composed of exons, that codes for protein. The region is bounded nearer the 5' end by a start codon and nearer the 3' end with a stop codon...
and deletion/duplication analysis) is available for isolated aniridia and the Gillespie syndrome. For the WAGR syndrome, high-resolution cytogenetic analysis and fluorescence in situ hybridization (FISH) can be utilized to identify deletions within chromosome band 11p13, where both the PAX6 and WT1 genes are located.
External links
- GeneReviews/NCBI/NIH/UW entry on Aniridia
- OMIM entries on Aniridia
- GeneReviews/NIH/NCBI/UW entry on Wilms Tumor Overview
- http://darned.ucc.ie
- Vision For Tomorrow - VFT
- The Aniridia Network
- Aniridia Foundation International - AFI
- Aniridia Europe
- Cure Aniridia - Funding and Finding a cure
Neethirajan G, Solomon A, Krishnadas SR, Vijayalakshmi P, Sundaresan P. (2009). "Genotype/phenotype association in Indian congenital aniridia".Indian J Pediatr 76 (5):513-517.PMID: 19390808