Leber's congenital amaurosis

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Leber's congenital amaurosis
Classification and external resources
Specialty Lua error in Module:Wikidata at line 446: attempt to index field 'wikibase' (a nil value).
ICD-10 H35.5
ICD-9-CM 362.76
OMIM 204000 204100 604232 604393 604537 605446 602225 604210 608553
DiseasesDB 33192
Patient UK Leber's congenital amaurosis
GeneReviews
[[[d:Lua error in Module:Wikidata at line 863: attempt to index field 'wikibase' (a nil value).|edit on Wikidata]]]

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] One form of LCA became well known in the scientific community following its successful treatment with gene therapy in 2008.[2][3][4][5]

LCA was first described by Theodor Leber in the 19th century.[6][7] It should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodor Leber.

Signs and symptoms

The term congenital refers to a condition present from birth (not acquired) and amaurosis refers to a loss of vision not associated with a lesion. However, beyond these general descriptions, the presentation of LCA can vary, because it is associated with multiple genes.[8][9]

LCA is typically characterized by nystagmus,[8] sluggish or absent pupillary responses,[9] and severe vision loss or blindness.[8]

Genetics

It is an autosomal recessive disorder thought to be caused by abnormal development of photoreceptor cells.[8]

OMIM currently recognizes 18 types of LCA:[8]

Type OMIM Gene Locus[8]
LCA1 204000 GUCY2D,[10] 17p13.1
LCA2 204100 RPE65[11] 1p31.3-p31.2
LCA3 609868 SPATA7 14q31.3
LCA4 604393 AIPL1[12][13] 17p13.2
LCA5 604537 LCA5[14] 6q14.1
LCA6 605446 RPGRIP1 14q11.2
LCA7 602225 CRX[15] 19q13.3
LCA8 604210 CRB1[15] 1q31-q32.1
LCA9 608553 NMNAT1[16][17][18][19] 1p36.22
LCA10 610142 CEP290 12q21.32
LCA11 146690 IMPDH1 7q32.1
LCA12 180040 RD3 7q32.1
LCA13 608830 RDH12 1q32.3
LCA14 604863 LRAT 14q24.1
LCA15 602280 TULP1 4q31
LCA16 603208 KCNJ13 2q37
LCA17 601147 GDF6 8q22
LCA18 179605 PRPH2 6p21

The gene CEP290 has been associated with Joubert syndrome, as well as type 10 LCA.[20]

Testing

Genetic tests and related research are currently being performed at Centogene AG in Rostock, Germany; University of Iowa John and Marcia Carver Nonprofit Genetic Testing Laboratory in Iowa City, IA; GENESIS Center for Medical Genetics in Poznan, Poland; Baylor College of Medicine Miraca Genetics Laboratories in Houston, TX; Asper Biotech in Tartu, Estonia; CGC Genetics in Porto, Portugal; CEN4GEN Institute for Genomics and Molecular Diagnostics in Edmonton, Canada; and Reference Laboratory Genetics - Barcelona, Spain.[21]

Treatment

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Main article: Adeno associated virus and gene therapy of the human retina

One form of LCA, patients with LCA2 bearing a mutation in the RPE65 gene, has been successfully treated by gene therapy in clinical trials. The results of three early clinical trials were published in 2008 demonstrating the safety and efficacy of adeno-associated virus to restore vision in LCA patients. In all three clinical trials, patients recovered functional vision without apparent side-effects.[2][3][4][5] These studies, which used adeno-associated virus, have spawned a number of new studies investigating gene therapy for human retinal disease.

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.[22] Early intervention was associated with better results.[22] 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.[22] 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.[23]

Eye Surgeon Dr. Al Maguire and gene therapy expert Dr. Jean Bennett developed the technique used by the Children's Hospital.[2][24]

Dr. Sue Semple-Rowland at the University of Florida has recently restored sight in an avian model using gene therapy.[25]

In Popular Culture

  • In the episode The Blackout in the Blizzard (season 6, episode 16) 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 named "Believe the Unseen") 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.
  • In the Korean drama The King of Dramas (episode 16, "In Search Of Lost Time") Anthony Kim, played by Kim Myung-min, is diagnosed with Leber's congenital amaurosis, the same disease that made his mother blind.
  • 4 year old Gavin who suffers from a form of LCA was made famous in 2013 by a YouTube video showing him using his white cane for the first time to navigate down a curb.[26]

See also

References

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  3. ↑ 3.0 3.1 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Leber's congenital amaurosis at Who Named It?
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Online 'Mendelian Inheritance in Man' (OMIM) LEBER CONGENITAL AMAUROSIS, TYPE I; LCA1 -204000
  9. ↑ 9.0 9.1 Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ 15.0 15.1 Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ 22.0 22.1 22.2 Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ https://www.youtube.com/watch?v=BsXa-mAKDVs

Further reading

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External links

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