Leber's congenital amaurosis

Leber's congenital amaurosis
Leber's congenital amaurosis
Classification and external resources
ICD-10 H53.0
ICD-9 362.76
OMIM 204000 204100
DiseasesDB 33192

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 Theodor Leber.

Contents

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 204000 GUCY2D 17p13.1
LCA2 204100 RPE65 1p31
LCA3 604232 RDH12 14q23.3
LCA4 604393 AIPL1 17p13.1
LCA5 604537 LCA5 6q14
LCA6 605446 RPGRIP1 14q11
LCA7 602225 CRX 19q13.3
LCA8 604210 CRB1 1q31-q32.1
LCA9 608553 LCA9 1p36
LCA10 610142 CEP290 12q21.33
LCA11 146690 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 Pittsburgh Pirates 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. He does indeed turn out to be a carrier, giving their unborn child a 25% chance of having LCA.
  • In the television series ER (season 14, episode 12) Dr. Abby Lockhart 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.

References

  1. ^ Stone EM (December 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. http://www.ajo.com/article/PIIS0002939407007672/. 
  2. ^ synd/1189 at Who Named It?
  3. ^ Leber T (1869). "Über Retinitis pigmentosa und angeborene Amaurose" (in German). Archiv für Ophthalmologie 15 (3): 1–25. doi:10.1007/BF02721213. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ a b Preising MN, Paunescu K, Friedburg C, Lorenz B (2007). "[Genetic and clinical heterogeneity in LCA patients. The end of uniformity]" (in German). Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft 104 (6): 490–8. doi:10.1007/s00347-007-1533-x. PMID 17525851. 
  7. ^ 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. 
  8. ^ "Inherited child blindness probed". BBC News. 2005-09-19. http://news.bbc.co.uk/2/hi/health/4250226.stm. Retrieved 2007-09-21. 
  9. ^ Online 'Mendelian Inheritance in Man' (OMIM) LEBER CONGENITAL AMAUROSIS, TYPE I; LCA1 -204000
  10. ^ 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. 
  11. ^ Genetic testing available for Leber's Congenital Amaurosis through Project 3000
  12. ^ "USATODAY.com - Orioles' Lee vows to fight daughter's rare disease". USA Today. 2006-09-29. http://www.usatoday.com/sports/baseball/nl/cubs/2006-09-29-lee-daughter_x.htm. Retrieved 2007-09-21. 
  13. ^ Maguire, A. M.; High, K. A.; Auricchio, A.; Wright, J. F.; Pierce, E. A.; Testa, F.; Mingozzi, F.; Bennicelli, J. L. et al. (2009). "Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial". The Lancet 374 (9701): 1597. doi:10.1016/S0140-6736(09)61836-5.  edit
  14. ^ Amado, D.; Mingozzi, F.; Hui, D.; Bennicelli, J. L.; Wei, Z.; Chen, Y.; Bote, E.; Grant, R. L. et al. (2010). "Safety and Efficacy of Subretinal Readministration of a Viral Vector in Large Animals to Treat Congenital Blindness". Science Translational Medicine 2 (21): 21ra16. doi:10.1126/scitranslmed.3000659. PMID 20374996. Lay summary – Physorg.com.  edit
  15. ^ "ABC News: Miracle Cure for Nearly Blind Youth". http://abcnews.go.com/GMA/Story?id=4739586&page=1. Retrieved 2008-04-27. 
  16. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2829748. 
  17. ^ Kaiser, Jocelyn; Voss, Stephen (January 2009). "Gene Therapy in a New Light". Smithsonian 39 (10): pp. 54–61. 

External links


Wikimedia Foundation. 2010.

Игры ⚽ Нужна курсовая?

Look at other dictionaries:

  • Leber's Congenital Amaurosis (LCA) and hallucinations —    The eponym Leber s congenital amaurosis refers to the German ophthalmologist Theodor Karl Gustav von Leber (1840 1917), who was the first to describe the concomitant condition in 1869. LCA is considered a type of amaurosis, due to an autosomal …   Dictionary of Hallucinations

  • Leber's congenital amaurosis — a hereditary disease (inherited as an autosomal recessive inherited condition) causing severe visual loss in infants. The back of the eye appears to be normal when examined with an ophthalmoscope, but marked abnormalities are found on the ERG… …   Medical dictionary

  • Leber's congenital amaurosis — a hereditary disease (inherited as an autosomal recessive condition) causing severe visual loss in infants. The fundus usually appears to be normal when examined with an ophthalmoscope, but marked abnormalities are found on the ERG (see… …   The new mediacal dictionary

  • Leber congenital amaurosis etc. — Le·ber congenital amaurosis, etc. (laґbər) [Theodor Leber, German ophthalmologist, 1840–1917] see Leber congenital amaurosis, under amaurosis, Hassall corpuscles, under corpuscle, and Hovius plexus, under plexus; and see under neuropathy …   Medical dictionary

  • Leber congenital amaurosis — a genetically heterogeneous, autosomal recessive disorder of the retina, characterized by severe or complete loss of vision that becomes apparent early in infancy, with absent or attenuated electroretinogram responses, inattention to visual… …   Medical dictionary

  • Leber's hereditary optic neuropathy — Classification and external resources ICD 10 H47.2 ICD 9 377.16 …   Wikipedia

  • Congenital fourth nerve palsy — Classification and external resources Trochlear nerve ICD 10 H49.1 …   Wikipedia

  • Amaurosis — (Greek meaning darkening, dark, or obscure) is vision loss or weakness that occurs without an apparent lesion affecting the eye.[1] It may result from either a medical condition or from excess acceleration, as in flight. The term is the same as… …   Wikipedia

  • Congenital hypothyroidism — Classification and external resources ICD 10 E00, E03.0, E03.1 …   Wikipedia

  • Congenital insensitivity to pain with anhidrosis — Classification and external resources OMIM 256800 DiseasesDB 32097 MeSH …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”