Leber congenital amaurosis: Difference between revisions
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==In Popular Culture== |
==In Popular Culture== |
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* In the episode [[The Blackout in the Blizzard]] of the television drama [[Bones]], Dr. Jack Hodgins and his pregnant wife Angela Montenegro, 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. |
* In the episode [[The Blackout in the Blizzard]] of the television drama [[Bones (TV show)|Bones]], Dr. Jack Hodgins and his pregnant wife Angela Montenegro, 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. |
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==References== |
==References== |
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Revision as of 21:57, 24 March 2011
| Leber congenital amaurosis | |
|---|---|
| Specialty | Ophthalmology  |
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.[1]
It was first described by Theodor Leber in the 19th century.[2][3] (It should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodore Leber.)
Presentation
Amaurosis 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.
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 GUCY2D,[4] and type 2 to RPE65.[5]
Other genes which have been implicated include CRB1,[6] CRX,[6] and AIPL1.[7][8]
OMIM currently recognizes 11 types of LCA:[9]
| Type | OMIM | Gene | Locus |
| LCA1 | Template:OMIM4 | GUCY2D | 17p13.1 |
| LCA2 | Template:OMIM4 | RPE65 | 1p31 |
| LCA3 | Template:OMIM4 | RDH12 | 14q23.3 |
| LCA4 | Template:OMIM4 | AIPL1 | 17p13.1 |
| LCA5 | Template:OMIM4 | LCA5 | 6q14 |
| LCA6 | Template:OMIM4 | RPGRIP1 | 14q11 |
| LCA7 | Template:OMIM4 | CRX | 19q13.3 |
| LCA8 | Template:OMIM4 | CRB1 | 1q31-q32.1 |
| LCA9 | Template:OMIM4 | LCA9 | 1p36 |
| LCA10 | Template:OMIM4 | CEP290 | 12q21.33 |
| LCA11 | Template:OMIM4 | IMPDH1 | 7q31.3-q32 |
The gene CEP290 has been associated with Joubert syndrome, as well as type 10 LCA.[10]
Testing
Project 3000, a foundation started by Baltimore Orioles 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.[11][12]
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.[citation needed]
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.[13] 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.[14]
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.[15][16][17]
In Popular Culture
- In the episode The Blackout in the Blizzard of the television drama Bones, Dr. Jack Hodgins and his pregnant wife Angela Montenegro, 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.
References
- ^ Stone EM (2007). "Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture". Am. J. Ophthalmol. 144 (6): 791–811. doi:10.1016/j.ajo.2007.08.022. PMID 17964524.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ synd/1189 at Who Named It?
- ^ Leber T (1869). "Über Retinitis pigmentosa und angeborene Amaurose". Archiv für Ophthalmologie (in German). 15 (3): 1–25. doi:10.1007/BF02721213.
- ^ Perrault I, Rozet JM, Calvas P; et al. (1996). "Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis". Nat. Genet. 14 (4): 461–4. doi:10.1038/ng1296-461. PMID 8944027.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Marlhens F, Bareil C, Griffoin JM; et al. (1997). "Mutations in RPE65 cause Leber's congenital amaurosis". Nat. Genet. 17 (2): 139–41. doi:10.1038/ng1097-139. PMID 9326927.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ a b Preising MN, Paunescu K, Friedburg C, Lorenz B (2007). "[Genetic and clinical heterogeneity in LCA patients. The end of uniformity]". Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft (in German). 104 (6): 490–8. doi:10.1007/s00347-007-1533-x. PMID 17525851.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Yzer S, Leroy BP, De Baere E; et al. (2006). "Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis". Invest. Ophthalmol. Vis. Sci. 47 (3): 1167–76. doi:10.1167/iovs.05-0848. PMID 16505055.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ "Inherited child blindness probed". BBC News. 2005-09-19. Retrieved 2007-09-21.
- ^ Online Mendelian Inheritance in Man (OMIM): LEBER CONGENITAL AMAUROSIS, TYPE I; LCA1 - 204000
- ^ Traboulsi EI, Koenekoop R, Stone EM (2006). "Lumpers or splitters? The role of molecular diagnosis in Leber congenital amaurosis". Ophthalmic Genet. 27 (4): 113–5. doi:10.1080/13816810601013146. PMID 17148037.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Genetic testing available for Leber's Congenital Amaurosis through Project 3000
- ^ "USATODAY.com - Orioles' Lee vows to fight daughter's rare disease". USA Today. 2006-09-29. Retrieved 2007-09-21.
- ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/S0140-6736(09)61836-5, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1016/S0140-6736(09)61836-5instead. - ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1126/scitranslmed.3000659, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1126/scitranslmed.3000659instead. - ^ "ABC News: Miracle Cure for Nearly Blind Youth".
{{cite web}}: Text "accessdate-2008-04-27" ignored (help) - ^ Maguire, Albert M., Simonelli, Francesca, Pierce, Eric A; et al. (2008). "Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis". N Engl J Med. 358 (21): 2240–2248. doi:10.1056/NEJMoa0802315. PMC 2829748. PMID 18441370.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Kaiser, Jocelyn; Voss, Stephen (January 2009). "Gene Therapy in a New Light". Smithsonian. Vol. 39, no. 10. pp. 54–61.
{{cite news}}:|access-date=requires|url=(help)CS1 maint: postscript (link)