Leber's congenital amaurosis
Encyclopedia
Leber's congenital amaurosis (LCA) is a rare inherited
eye disease that appears at birth or in the first few months of life, and affects around 1 in 80,000 of the population.
It was first described by Theodor Leber
in the 19th century. It should not be confused with Leber's hereditary optic neuropathy
, which is a different disease also described by Theodor Leber.
refers to a loss of vision not associated with a lesion
, and congenital refers to a condition present from birth (not acquired). However, beyond these general descriptions, the presentation of LCA can vary, because it is associated with multiple genes.
LCA is typically characterized by nystagmus, sluggish or no pupillary responses
, and severe vision loss
or blindness
.
There is evidence tying type 1 LCA to , and type 2 to .
Other genes which have been implicated include , , and .
OMIM currently recognizes 11 types of LCA:
The gene has been associated with Joubert syndrome
, as well as type 10 LCA.
first baseman
Derrek Lee
and Boston Celtics
owner Wyc Grousbeck
, works to have the approximately 3,000 people in the United States
with the disease
genetically tested.
Genetic tests and research are currently being performed at the University of Iowa
Carver Lab by Drs. Edwin Stone and Val Sheffield. Dr. Sue Rowland at the University of Florida has recently restored sight in an avian model using gene therapy
.
Researchers at Children's Hospital of Philadelphia
and the University of Pennsylvania
have treated six young people via gene therapy. Eye Surgeon Dr. Al Maguire and gene therapy expert Dr. Jean Bennett developed the technique used by the Children's Hospital.
Heredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...
eye disease that appears at birth or in the first few months of life, and affects around 1 in 80,000 of the population.
It was first described by Theodor Leber
Theodor Leber
Theodor Karl Gustav von Leber was a German ophthalmologist from Karlsruhe.Leber was a student of Hermann von Helmholtz in Heidelberg, where he received his doctorate in 1862...
in the 19th century. It should not be confused with Leber's hereditary optic neuropathy
Leber's hereditary optic neuropathy
Leber’s hereditary optic neuropathy or Leber optic atrophy is a mitochondrially inherited degeneration of retinal ganglion cells and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males...
, which is a different disease also described by Theodor Leber.
Presentation
AmaurosisAmaurosis
Amaurosis is vision loss or weakness that occurs without an apparent lesion affecting the eye. It may result from either a medical condition or from excess acceleration, as in flight...
refers to a loss of vision not associated with a lesion
Lesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
, and congenital refers to a condition present from birth (not acquired). However, beyond these general descriptions, the presentation of LCA can vary, because it is associated with multiple genes.
LCA is typically characterized by nystagmus, sluggish or no pupillary responses
Pupillary reflex
The pupillary light reflex is a reflex that controls the diameter of the pupil, in response to the intensity of light that falls on the retina of the eye, thereby assisting in adaptation to various levels of darkness and light, in addition to retinal sensitivity...
, and severe vision loss
Vision loss
Vision loss or visual loss is the absence of vision where it existed before, which can happen either acutely or chronically .-Ranges of vision loss:...
or blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
.
Genetics
It is an autosomal recessive disorder thought to be caused by abnormal development of photoreceptor cells.There is evidence tying type 1 LCA to , and type 2 to .
Other genes which have been implicated include , , and .
OMIM currently recognizes 11 types of LCA:
| Type | OMIM | Gene Gene A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains... |
Locus Locus (genetics) In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map... >- | LCA1 |
GUCY2D GUCY2D GUCY2D is a guanylate cyclase associated with type 1 Leber's congenital amaurosis.-References:... |
>- | RPE65 RPE65 Retinal pigment epithelium-specific 65 kDa protein is a protein that in humans is encoded by the RPE65 gene.-Function:The retinal pigment epithelium-specific 65 kDa protein is located in the retinal pigment epithelium and is involved in the conversion of all-trans retinol to 11-cis retinal during... |
>- | RDH12 RDH12 Retinol dehydrogenase 12 is an enzyme that in humans is encoded by the RDH12 gene.-Further reading:... |
>- | AIPL1 AIPL1 Aryl-hydrocarbon-interacting protein-like 1 is a protein that in humans is encoded by the AIPL1 gene.-External links:*... |
>- | LCA5 LCA5 Lebercilin, also known as leber congenital amaurosis 5 , is a protein that in humans is encoded by the LCA5 gene. This protein is thought to be involved in centrosomal or ciliary functions.- Clinical significance :... |
>- | RPGRIP1 RPGRIP1 X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 is an enzyme that in humans is encoded by the RPGRIP1 gene.-Interactions:RPGRIP1 has been shown to interact with Retinitis pigmentosa GTPase regulator.-Further reading:... |
>- | CRX CRX (gene) Cone-rod homeobox protein is a protein that in humans is encoded by the CRX gene.-External links:*... |
>- | CRB1 CRB1 Crumbs homolog 1 is a protein that in humans is encoded by the CRB1 gene.This gene encodes a protein which is similar to the Drosophila crumbs protein and localizes to the inner segment of mammalian photoreceptors... |
>- | LCA9 LCA9 LCA9 is a gene associated with Leber's congenital amaurosis.... |
>- | CEP290 CEP290 Centrosomal protein of 290 kDa is a protein that in humans is encoded by the CEP290 gene.-External Links:* -Further reading:... |
>- | IMPDH1 IMPDH1 Inosine-5'-monophosphate dehydrogenase 1, also known as IMP dehydrogenase 1, is an enzyme that in humans is encoded by the IMPDH1 gene.- Function :... |
7q31.3-q32 |
The gene has been associated with Joubert syndrome
Joubert syndrome
Joubert syndrome is a rare genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination.-Diagnosis:...
, as well as type 10 LCA.
Testing
Project 3000, a foundation started by Pittsburgh PiratesPittsburgh Pirates
The Pittsburgh Pirates are a Major League Baseball club based in Pittsburgh, Pennsylvania. They play in the Central Division of the National League, and are five-time World Series Champions...
first baseman
First baseman
First base, or 1B, is the first of four stations on a baseball diamond which must be touched in succession by a baserunner in order to score a run for that player's team...
Derrek Lee
Derrek Lee
Derrek Leon Lee , or "D-Lee", is a Major League Baseball first baseman. Lee has played with the San Diego Padres , the Florida Marlins , Chicago Cubs , Atlanta Braves , Baltimore Orioles and Pittsburgh Pirates . He bats and throws right-handed.Lee was a World Series Champion with Florida in 2003,...
and Boston Celtics
Boston Celtics
The Boston Celtics are a National Basketball Association team based in Boston, Massachusetts. They play in the Atlantic Division of the Eastern Conference. Founded in 1946, the team is currently owned by Boston Basketball Partners LLC. The Celtics play their home games at the TD Garden, which...
owner Wyc Grousbeck
Wycliffe Grousbeck
Wycliffe "Wyc" Grousbeck is CEO, governor, and co-owner of the National Basketball Association's Boston Celtics.After spending seven years as a partner at a venture capital firm, Highland Capital Partners, Grousbeck founded the group Boston Basketball Partners L.L.C...
, works to have the approximately 3,000 people in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
with the disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
genetically tested.
Genetic tests and research are currently being performed at the University of Iowa
University of Iowa
The University of Iowa is a public state-supported research university located in Iowa City, Iowa, United States. It is the oldest public university in the state. The university is organized into eleven colleges granting undergraduate, graduate, and professional degrees...
Carver Lab by Drs. Edwin Stone and Val Sheffield. Dr. Sue Rowland at the University of Florida has recently restored sight in an avian model using gene therapy
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
.
Treatment
Gene therapy treatments are still in the trial phase but there have been successes. The results of a phase 1 trial conducted, by the University of Pennsylvania and Children’s Hospital of Philadelphia and published in 2009, showed sustained improvement in 12 subjects (ages 8 to 44) with RPE65-associated LCA after treatment with AAV2-hRPE65v2, a gene replacement therapy. Early intervention was associated with better results. In that study patients were excluded based on the presence of particular antibodies to the vector AAV2 and treatment was only administered to one eye as a precaution. A 2010 study testing the effect of administration of AAV2-hRPE65v2 in both eyes in animals with antibodies present suggested that immune responses may not complicate use of the treatment in both eyes.Researchers at Children's Hospital of Philadelphia
Children's Hospital of Philadelphia
The Children's Hospital of Philadelphia is one of the largest and oldest children's hospitals in the world. CHOP has been ranked as the best children's hospital in the United States by U.S. News & World Report and Parents Magazine in recent years. As of 2008, it was ranked #1 in the nation for...
and the University of Pennsylvania
University of Pennsylvania
The University of Pennsylvania is a private, Ivy League university located in Philadelphia, Pennsylvania, United States. Penn is the fourth-oldest institution of higher education in the United States,Penn is the fourth-oldest using the founding dates claimed by each institution...
have treated six young people via gene therapy. Eye Surgeon Dr. Al Maguire and gene therapy expert Dr. Jean Bennett developed the technique used by the Children's Hospital.
In Popular Culture
- In the episode The Blackout in the Blizzard of the television drama BonesBones (TV series)Bones is an American crime drama television series that premiered on the Fox Network on September 13, 2005. The show is based on forensic anthropology and forensic archaeology, with each episode focusing on an FBI case file concerning the mystery behind human remains brought by FBI Special Agent...
, Dr. Jack HodginsJack Hodgins (Bones)Dr. Jack Stanley Hodgins IV, Ph.D., is a fictional character in the American television series, Bones. He is portrayed by T. J. Thyne. Jack is introduced to the series primarily as an entomologist/forensic entomologist, but also as a mineralogist/forensic mineralogist, a palynology/forensic...
and his pregnant wife Angela MontenegroAngela MontenegroAngela Pearly-Gates Montenegro Hodgins is a fictional character in the television series Bones , portrayed by Michaela Conlin...
, who is an LCA carrier, have to wait during a citywide blackout for Hodgins's genetic test results, to see if he is also an LCA carrier. He does indeed turn out to be a carrier, giving their unborn child a 25% chance of having LCA. - In the television series ERER (TV series)ER is an American medical drama television series created by novelist Michael Crichton that aired on NBC from September 19, 1994 to April 2, 2009. It was produced by Constant c Productions and Amblin Entertainment, in association with Warner Bros. Television...
(season 14, episode 12) Dr. Abby LockhartAbby LockhartDr. Abby Lockhart is a fictional medical doctor on the television series ER. She is portrayed by Maura Tierney...
diagnoses a young foster girl with Leber's congenital amaurosis. The girl to this point hid her condition from her foster families. The episode contains some information about symptoms, clinical diagnosis and mentions gene replacement therapy and clinical trials as hope for help in managing the condition.